SULFUR COMPOUNDS AND PROCESSES AND INTERMEDIATES USEFUL IN THE PREPARATION THEREOF INTRODUCTION [001] The present application provides novel sulfondiimidamide compounds, mild and versatile processes for the preparation of sulfondiimidamide compounds and intermediates useful in said processes. BACKGROUND OF THE INVENTION [002] Sulfur(VI) compounds have played a substantial role in the development of medicines. Sulfones and sulfonamides in particular are key components of numerous drugs as well as agrochemicals ¹ . Replacing one of the oxygen atoms in these molecules with a nitrogen atom gives sulfoximines ² and sulfonimidamides ³ respectively. [003] Sulfoximines and sulfonimidamides have recently gained traction in medicinal chemistry,first as isosteric replacements for their oxygenated analogues ⁴ , and more recently due to increasing recognition of their potent mix of physicochemical properties. Being inherently chiral at sulfur, polar, and three-dimensional, with good aqueous solubility and high chemical and metabolic stability ⁵ , sulfoximines and sulfonimidamides represent an invaluable addition to the medicinal chemist’s toolbox ⁶ . [004] Considerable advances have been made in recent years in the synthesis of sulfoximines and sulfonimidamides by the Bolm and Bull groups, as well as others, which have simplified the imination of thioethers ⁷ , sulfoxides ⁸ , and sulfenamides ⁹ . [005] However, to date there have been no reports of a mild and versatile route to obtain sulfondiimidamides which are obtained when the oxygen atom in a sulfonimidamides is replaced with a nitrogen atom. [006] It is envisaged that a mild and verstaile route to sulfondiimidamide compounds would provide access to sulfondiimidamide compound libraries useful for screening against biological targets and/or provide a means of accessing compounds potentially bio-isosteric to sulfonimidamides with known biological activity which may enable further optimisation of potency, physiochemical and pharmacokinetic properties. [007] There is a need for further diversity in a chemist’s toolbox. The present invention provides novel sulfondiimidamide compounds, mild and versatile processes for the preparation of sulfondiimidamide compounds and intermediates useful in said processes. SUMMARY OF THE INVENTION [008] In one aspect, the present invention provides a process for preparing a compound of formula I, or a salt thereof: (I), comprising: (i) deprotecting a compound of formula II: (II), to yield a compound of formula Ia: (Ia); and/or (ii) reacting a compound of formula Ia with a reactant suitable for introducing group R ³ to give a compound of formula Ib: (Ib), and/or (iii) deprotecting a compound of formula Ib to yield a compound of formula Ic: (Ic); and/or (iv) and reacting a compound of formula Ic with a reactant suitable for introducing group R ⁴ to give a compound of formula I; and (v) optionally preparing a salt of formula I; wherein R, R ¹ , R ² , R ³ , R ⁴ , P ² and P ³ are defined herein. [009] In another aspect, the present invention provides a compound of Formula I, or a salt thereof: (I) as defined herein. [0010] In another aspect, the present invention provides a compound of Formula II, or a salt thereof: as defined herein. [0011] In another aspect, the present invention provides a process for preparing a compound of formula II (II), comprising reacting a compound of formula (III): (III), with a compound of formula (IV): H-NR1R2 (IV); wherein R, R ¹ , R ² , P ² and P ³ are defined herein. [0012] In another aspect, the present invention provides a compound of formula III, or a salt thereof: (III), as defined herein. [0013] In another aspect, the present invention provides a process for preparing a compound of formula III: (III), comprising reaction a compound of formula V: (V), with a halogenating agent; [0014] In another aspect, the present invention provides a compound of formula V, or a salt thereof:

(V), as defined herein. [0015] In another aspect, the present invention provides a process for the preparation of a compound of formula V: (V), comprising protecting a compound of formula VI: (VI), with a nitrogen protecting group P ³ . [0016] In another aspect, the present invention provides a compound of formula VI, or a salt thereof: (VI), as defined herein. [0017] In another aspect, the present invention provides a process for the preparation of a compound of formula VI: (VI), comprising reacting a compound of formula VII: with a compound of formula VIII: R-M (VIII). [0018] In another aspect, the present invention provides a compound of formula Ic, or a salt thereof: (Ic), as defined herein. [0019] In another aspect, the present invention provides a compound of formula Ib, or a salt thereof: (Ib), as defined herein. [0020] In another aspect, the present invention provides a compound of formula Ia, or a salt thereof: (Ia), as defined herein. [0021] Preferred, suitable, and optional features of any one particular aspect of the present invention are also preferred, suitable, and optional features of any other aspect. DETAILED DESCRIPTION OF THE INVENTION Definitions [0022] The compounds and intermediates described herein may be named according to either the IUPAC (International Union for Pure and Applied Chemistry) or CAS (Chemical Abstracts Service) nomenclature systems. [0023] The various hydrocarbon-containing moieties provided herein may be described using a prefix designating the minimum and maximum number of carbon atoms in the moiety, e.g. “(C _a - _b )” or “C _a -C _b ” or “(a-b)C”. For example, (C _a - _b )alkyl indicates an alkyl moiety having the integer “a” to the integer “b” number of carbon atoms, inclusive. Certain moieties may also be described according to the minimum and maximum number of members with or without specific reference to a particular atom or overall structure. For example, the terms “a to b membered ring” or “having between a to b members” refer to a moiety having the integer “a” to the integer “b” number of atoms, inclusive. [0024] "About" when used herein in conjunction with a measurable value such as, for example, an amount or a period of time or temperature and the like, is meant to encompass reasonable variations of the value, for instance, to allow for experimental error in the measurement of said value. [0025] As used herein by themselves or in conjunction with another term or terms, "alkyl" and “alkyl group” refer to a branched or unbranched saturated hydrocarbon chain. Unless specified otherwise, alkyl groups typically contain 1-10 carbon atoms, such as 1-6 carbon atoms or 1-4 carbon atoms or 1-3 carbon atoms, and can be substituted or unsubstituted. Representative examples include, but are not limited to, methyl, ethyl, n-propyl, i-propyl, n- butyl, i-butyl, s-butyl, t-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, isopropyl, tert-butyl, isobutyl, etc. [0026] As used herein by themselves or in conjunction with another term or terms, “alkylene” and “alkylene group” refer to a branched or unbranched saturated hydrocarbon chain. Unless specified otherwise, alkylene groups typically contain 1-10 carbon atoms, such as 1-6 carbon atoms or 1-3 carbon atoms, and can be substituted or unsubstituted. Representative examples include, but are not limited to, methylene (–CH ₂ –), the ethylene isomers (–CH(CH ₃ )– and – CH ₂ CH ₂ –), the propylene isomers (–CH(CH ₃ )CH ₂ –, –CH(CH ₂ CH ₃ )–, –C(CH ₃ ) ₃ –, and – CH ₂ CH ₂ CH ₂ –), etc. [0027] As used herein by themselves or in conjunction with another term or terms, “alkenyl” and “alkenyl group” refer to a branched or unbranched hydrocarbon chain containing at least one double bond. Unless specified otherwise, alkenyl groups typically contain 2-10 carbon atoms, such as 2-6 carbon atoms or 2-4 carbon atoms, and can be substituted or unsubstituted. Representative examples include, but are not limited to, ethenyl, 3-buten-1-yl, 2-ethenylbutyl, and 3-hexen-1-yl. [0028] As used herein by themselves or in conjunction with another term or terms, “alkynyl” and “alkynyl group” refer to a branched or unbranched hydrocarbon chain containing at least one triple bond. Unless specified otherwise, alkynyl groups typically contain 2-10 carbon atoms, such as 2-6 carbon atoms or 2-4 carbon atoms, and can be substituted or unsubstituted. Representative examples include, but are not limited to, ethynyl, 3-butyn-1-yl, propynyl, 2-butyn-1-yl, and 3-pentyn-1-yl. [0029] As used herein by itself or in conjunction with another term or terms, “aromatic” refers to monocyclic and polycyclic ring systems containing 4n+2 pi electrons, where n is an integer. Aromatic should be understood as referring to and including ring systems that contain only carbon atoms (i.e. “aryl”) as well as ring systems that contain at least one heteroatom selected from N, O or S (i.e. “heteroaromatic” or “heteroaryl”). An aromatic ring system can be substituted or unsubstituted. [0030] As used herein by itself or in conjunction with another term or terms, “non-aromatic” refers to a monocyclic or polycyclic ring system having at least one double bond that is not part of an extended conjugated pi system. As used herein, non-aromatic refers to and includes ring systems that contain only carbon atoms as well as ring systems that contain at least one heteroatom selected from N, O or S. A non-aromatic ring system can be substituted or unsubstituted. [0031] As used herein by themselves or in conjunction with another term or terms, “aryl” and “aryl group” refer to phenyl or polycyclic hydrocarbon ring systems, including bridged, spiro, and/or fused ring systems, in which at least one of the rings is aromatic. Aryl groups can be substituted or unsubstituted. Unless specified otherwise, an aryl group may contain 6 ring atoms (i.e., phenyl) or a ring system containing 9 to 15 atoms, such as 9 to 11 ring atoms, or 9 or 10 ring atoms. Representative examples include, but are not limited to, naphthyl, indenyl, indanyl, 1,2,3,4-tetrahydronaphthalenyl, 6,7,8,9-tetrahydro-5H-benzocycloheptenyl, and 6,7,8,9-tetrahydro-5H-benzocycloheptenyl. Suitably an aryl group is phenyl or naphthyl, suitably phenyl. [0032] As used herein by themselves or in conjunction with another term or terms, “arylene” and “arylene group” refer to a phenylene (–C ₆ H ₄ –) or to 7 to 15 membered bicyclic or tricyclic hydrocarbon ring systems, including bridged, spiro, and/or fused ring systems, in which at least one of the rings is aromatic. Arylene groups can be substituted or unsubstituted. In some embodiments, an arylene group may contain 6 (i.e., phenylene) ring atoms or be a ring system containing 9 to 15 atoms; such as 9 to 11 ring atoms; or 9 or 10 ring atoms. Arylene groups can be substituted or unsubstituted. [0033] As used herein by themselves or in conjunction with another term or terms, “arylalkyl” and “arylalkyl group” refer to an alkyl group in which a hydrogen atom is replaced by an aryl group, wherein alkyl group and aryl group are as previously defined, such as, for example, benzyl (C ₆ H ₅ CH ₂ –). Arylalkyl groups can be substituted or unsubstituted. [0034] As used herein by themselves or in conjunction with another term or terms, “carbocyclic group” and “carbocycle” refer to monocyclic and polycyclic ring systems that contain only carbon atoms in the ring(s), i.e., hydrocarbon ring systems, without regard or reference to aromaticity or degree of unsaturation. Thus, carbocyclic group should be understood as referring to and including ring systems that are fully saturated (such as, for example, a cyclohexyl group), ring systems that are aromatic (such as, for example, a phenyl group), as well as ring systems having fully saturated, aromatic and/or unsaturated portions (such as, for example, cyclohexenyl, 2,3-dihydro-indenyl, and 1,2,3,4-tetrahydro- naphthalenyl). The terms carbocyclic and carbocycle further include bridged, fused, and spirocyclic ring systems. [0035] As used herein by themselves or in conjunction with another term or terms, “cycloalkyl” and “cycloalkyl group” refer to a non-aromatic carbocyclic ring system, that may be monocyclic, bicyclic, or tricyclic, saturated or unsaturated, and may be bridged, spiro, and/or fused. A cycloalkyl group may be substituted or unsubstituted. Unless specified otherwise, a cycloalkyl group typically contains from 3 to 12 ring atoms. In some instances a cycloalkyl group may contain 4 to 10 ring atoms (e.g., 4 ring atoms, 5 ring atoms, 6 ring atoms, 7 ring atoms, etc.). Representative examples include, but are not limited to, cyclopropyl, cyclopropenyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, norbornyl, norbornenyl, bicyclo[2.2.1]hexane, bicyclo[2.2.1]heptane, bicyclo[2.2.1]heptene, bicyclo[3.1.1]heptane, bicyclo[3.2.1]octane, bicyclo[2.2.2]octane, bicyclo[3.2.2]nonane, bicyclo[3.3.1]nonane, and bicyclo[3.3.2]decane. Suitably, cycloalkyl groups are selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl groups. [0036] As used herein by themselves or in conjunction with another term or terms, “cycloalkylalkyl” and “cycloalkylalkyl group” refer to an alkyl group in which a hydrogen atom is replaced by a cycloalkyl group, wherein alkyl group and cycloalkyl group are as previously defined, such as, for example, cyclohexylmethyl (C ₆ H ₁₁ CH ₂ –). Cycloalkylalkyl groups can be substituted or unsubstituted. [0037] As used herein by themselves or in conjunction with another term or terms, “haloalkyl” and “haloalkyl group” refer to alkyl groups in which one or more hydrogen atoms are replaced by halogen atoms. Haloalkyl includes both saturated alkyl groups as well as unsaturated alkenyl and alkynyl groups. Representative examples include, but are not limited to, –CF ₃ , – CHF ₂ , –CH ₂ F, –CF ₂ CF ₃ , –CHFCF ₃ , –CH ₂ CF ₃ , –CF ₂ CH ₃ , –CHFCH ₃ , –CF ₂ CF ₂ CF ₃ , – CF ₂ CH ₂ CH ₃ , –CF=CF ₂ , –CCl=CH ₂ , –CBr=CH ₂ , –CI=CH ₂ , –C≡C-CF ₃ , –CHFCH ₂ CH ₃ and – CHFCH ₂ CF ₃ . Haloalkyl groups can be substituted or unsubstituted. Suitably, a haloalkyl group is selected from CHF2 and CF3, suitably CF3. [0038] As used herein by themselves or in conjunction with another term or terms, “haloalkoxy” and “haloalkoxy group” refer to alkoxy groups (i.e. O-alkyl groups) in which one or more hydrogen atoms are replaced by halogen atoms. Haloalkoxy includes both saturated alkoxy groups as well as unsaturated alkenyl and alkynyl groups. Representative examples include, but are not limited to, –OCF3, –OCHF2, –OCH2F, –OCF2CF3, –OCHFCF3, –OCH2CF3, –OCF2CH3, –OCHFCH3, –OCF2CF2CF3, –OCF2CH2CH3, –OCF=CF2, –OCCl=CH2, – OCBr=CH2, –OCHFCH2CH3 and –OCHFCH2CF3. Haloalkoxy groups can be substituted or unsubstituted. Suitably, a haloalkyoxy group is selected from –OCHF2 and –OCF3, suitably – OCF3. [0039] As used herein by themselves or in conjunction with another term or terms, “halo” and “halogen” include fluorine, chlorine, bromine and iodine atoms and substituents. [0040] As used herein by themselves or in conjunction with another term or terms, “heteroaryl” and “heteroaryl group” refer to (a) 5 and 6 membered monocyclic aromatic rings, which contain, in addition to carbon atom(s), at least one heteroatom, such as nitrogen, oxygen or sulfur, and (b) 7 to15 membered bicyclic and tricyclic rings, which contain, in addition to carbon atom(s), at least one heteroatom, such as nitrogen, oxygen or sulfur, and in which at least one of the rings is aromatic. In some instances, a heteroaryl group can contain two or more heteroatoms, which may be the same or different. Heteroaryl groups can be substituted or unsubstituted, and may be bridged, spiro, and/or fused. In some instances, a heteroaryl group may contain 5, 6, or 8 to 15 ring atoms. In other instances, a heteroaryl group may contain 5 to 10 ring atoms, such as 5, 6, 9, or 10 ring atoms. Representative examples include, but are not limited to, 2,3-dihydrobenzofuranyl, 1,2-dihydroquinolinyl, 3,4-dihydroisoquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4-tetrahydroquinolinyl, benzoxazinyl, benzthiazinyl, chromanyl, furanyl, 2-furanyl, 3-furanyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, oxazolyl, pyridinyl, 2-, 3-, or 4-pyridinyl, pyrimidinyl, 2-, 4-, or 5-pyrimidinyl, pyrazolyl, pyrrolyl, 2- or 3-pyrrolyl, pyrazinyl, pyridazinyl, 3- or 4-pyridazinyl, 2-pyrazinyl, thienyl, 2-thienyl, 3- thienyl, tetrazolyl, thiazolyl, thiadiazolyl, triazinyl, triazolyl, pyridin-2-yl, pyridin-4-yl, pyrimidin- 2-yl, pyridazin-4-yl, pyrazin-2-yl, naphthyridinyl, pteridinyl, phthalazinyl, purinyl, alloxazinyl, benzimidazolyl, benzofuranyl, benzofurazanyl, 2H-1-benzopyranyl, benzothiadiazine, benzothiazinyl, benzothiazolyl, benzothiophenyl, benzoxazolyl, cinnolinyl, furopyridinyl, indolinyl, indolizinyl, indolyl, or 2-, 3-, 4-, 5-, 6-, or 7-indolyl, 3H-indolyl, quinazolinyl, quinoxalinyl, isoindolyl, isoquinolinyl, 10-aza-tricyclo[6.3.1.0 ^2,7 ]dodeca-2(7),3,5-trienyl, 12- oxa-10-aza-tricyclo[6.3.1.0 ^2,7 ]dodeca-2(7),3,5-trienyl, 12-aza-tricyclo[7.2.1.0 ^2,7 ]dodeca- 2(7),3,5-trienyl, 10-aza-tricyclo[6.3.2.0 ^2,7 ]trideca-2(7),3,5-trienyl, 2,3,4,5-tetrahydro-1H- benzo[d]azepinyl, 1,3,4,5-tetrahydro-benzo[d]azepin-2-onyl, 1,3,4,5-tetrahydro- benzo[b]azepin-2-onyl, 2,3,4,5-tetrahydro-benzo[c]azepin-1-onyl, 1,2,3,4-tetrahydro- benzo[e][1,4]diazepin-5-onyl, 2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepinyl, 5,6,8,9- tetrahydro-7-oxa-benzocycloheptenyl, 2,3,4,5-tetrahydro-1H-benzo[b]azepinyl, 1,2,4,5- tetrahydro-benzo[e][1,3]diazepin-3-onyl, 3,4-dihydro-2H-benzo[b][1,4]dioxepinyl, 3,4-dihydro- 2H-benzo[f][1,4]oxazepin-5-onyl, 6,7,8,9-tetrahydro-5-thia-8-aza-benzocycloheptenyl, 5,5- dioxo-6,7,8,9-tetrahydro-5-thia-8-aza-benzocycloheptenyl, and 2,3,4,5-tetrahydro- benzo[f][1,4]oxazepinyl. Suitably, a heteroaryl is a 5- or 6-membered heteroaryl ring comprising one, two or three heteroatoms selected from N, O or S. [0041] As used herein by themselves or in conjunction with another term or terms, “heteroarylalkyl” and “heteroarylalkyl group” refer to an alkyl group in which a hydrogen atom is replaced by a heteroaryl group, wherein alkyl group and heteroaryl group are as previously defined. Heteroarylalkyl groups can be substituted or unsubstituted. Where carbon numbers are provided, e.g. heteroaryl(Cn-m)alkyl, the range refers to the alkyl group. Suitably, the constituent alkyl group has 1-6 carbons, suitable 1-3 carbons. [0042] As used herein by themselves or in conjunction with another term or terms, “heterocyclic group” and “heterocycle” refer to monocyclic and polycyclic ring systems that contain carbon atoms and at least one heteroatom selected from nitrogen, oxygen, sulfur or phosphorus in the ring(s), without regard or reference to aromaticity or degree of unsaturation. Thus, a heterocyclic group should be understood as referring to and including ring systems that are fully saturated (such as, for example, a piperidinyl group), ring systems that are aromatic (such as, for example, a pyrindinyl group), as well as ring systems having fully saturated, aromatic and/or unsaturated portions (such as, for example, 1,2,3,6- tetrahydropyridinyl and 6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrizinyl). The terms heterocyclic and heterocycle further include bridged, fused, and spirocyclic ring systems. [0043] As used herein by themselves or in conjunction with another term or terms, “heterocycloalkyl” and “heterocycloalkyl group” refer to 3 to15 membered monocyclic, bicyclic, and tricyclic non-aromatic ring systems, which contain, in addition to carbon atom(s), at least one heteroatom, such as nitrogen, oxygen, sulfur or phosphorus. Heterocycloalkyl groups may be fully saturated or contain unsaturated portions and may be bridged, spiro, and/or fused ring systems. In some instances a heterocycloalkyl group may contain at least two or heteroatoms, which may be the same or different. Heterocycloalkyl groups can be substituted or unsubstituted. In some instances a heterocycloalkyl group may contain from 3 to 10 ring atoms or from 3 to 7 ring atoms or from 5 to 7 ring atoms, such as 5 ring atoms, 6 ring atoms, or 7 ring atoms. Representative examples include, but are not limited to, tetrahydrofuranyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidyl, piperazinyl, indolinyl, isoindolinyl, morpholinyl, thiomorpholinyl, homomorpholinyl, homopiperidyl, homopiperazinyl, thiomorpholinyl-5-oxide, thiomorpholinyl-S,S-dioxide, pyrrolidinyl, tetrahydropyranyl, piperidinyl, tetrahydrothienyl, homopiperidinyl, homothiomorpholinyl-S,S-dioxide, oxazolidinonyl, dihydropyrazolyl, dihydropyrrolyl, dihydropyrazinyl, dihydropyridinyl, dihydropyrimidinyl, dihydrofuryl, dihydropyranyl, tetrahydrothienyl-5-oxide, tetrahydrothienyl-S,S-dioxide, homothiomorpholinyl-5-oxide, quinuclidinyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 8-oxa-3-aza-bicyclo[3.2.1]octanyl, 3,8-diaza- bicyclo[3.2.1]octanyl, 2,5-diaza-bicyclo[2.2.1]heptanyl, 3,8-diaza-bicyclo[3.2.1]octanyl, 3,9- diaza-bicyclo[4.2.1]nonanyl, 2,6-diaza-bicyclo[3.2.2]nonanyl, [1,4]oxaphosphinanyl- 4-oxide, [1,4]azaphosphinanyl- 4-oxide, [1,2]oxaphospholanyl- 2-oxide, phosphinanyl-1-oxide, [1,3]azaphospholidinynl- 3-oxide, [1,3]oxaphospholanyl- 3-oxide, 7-oxabicyclo[2.2.1]heptanyl, 6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl, 6,8-dihydro-5H-imidazo[1,5-a]pyrazin-7-yl, 6,8-dihydro-5H-imidazo[1,2-a]pyrazin-7-yl, 5,6,8,9-tetrahydro-[1,2,4]triazolo[4,3- d][1,4]diazepin-7-yl and 6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl. Suitably, a heterocyclylalkyl group as defined herein is a monocyclic, bicyclic or spiro heterocyclyl group comprising one, two or three heteroatoms selected from N, O or S. [0044] As used herein by themselves or in conjunction with another term or terms, “heterocycloalkylene” and “heterocycloalkylene group” refer to 3 to15 membered monocyclic, bicyclic, or tricyclic non-aromatic ring systems, which contain, in addition to carbon atom(s), at least one heteroatom, such as nitrogen, oxygen, sulfur or phosphorus. Heterocycloalkylene groups may be fully saturated or contain unsaturated portions and may be bridged, spiro, and/or fused. Heterocycloalkylene groups can be substituted or unsubstituted. In some instances, a heterocycloalkylene group may contain from 3 to 10 ring atoms; such as from 3 to 7 ring atoms. In other instances a heterocycloalkylene group may contain from 5 to 7 ring atoms, such as 5 ring atoms, 6 ring atoms, or 7 ring atoms. [0045] As used herein by themselves or in conjunction with another term or terms, “heterocycloalkylalkyl” and “heterocycloalkylalkyl group” refer to an alkyl group in which a hydrogen atom is replaced by a heterocycloalkyl group, wherein alkyl group and heterocycloalkyl group are as previously defined, such as, for example, pyrrolidinylmethyl (C ₄ H ₈ NCH ₂ –). Heteroycloalkylalkyl groups can be substituted or unsubstituted. Where carbon numbers are provided, e.g. heterocycloalkyl(C _n - _m )alkyl, the range refers to the alkyl group. Suitably, the constituent alkyl group has 1-6 carbons, suitable 1-3 carbons. [0046] As used herein by themselves or in conjunction with another term or terms, “stable” and “chemically stable” refer to a compound that is sufficiently robust to be isolated from a reaction mixture with a useful degree of purity. The present application is directed solely to the preparation of stable compounds. When lists of alternative substituents include members which, owing to valency requirements, chemical stability, or other reasons, cannot be used to substitute a particular group, the list is intended to be read in context to include those members of the list that are suitable for substituting the particular group. For example, when considering the degree of optional substitution of a particular moiety, it should be understood that the number of substituents does not exceed the valency appropriate for that moiety. For example, if R ¹ is a methyl group (-CH3), it can be optionally substituted by 1 to 3 groups. [0047] As used herein by itself or in conjunction with another term or terms, “substituted” indicates that a hydrogen atom on a molecule has been replaced with a different atom or group of atoms and the atom or group of atoms replacing the hydrogen atom is a “substituent.” It should be understood that the terms “substituent”, “substituents”, “moiety”, “moieties”, “group”, or “groups” refer to substituent(s). [0048] As used herein “protecting group” refers to a functional group that facilitates chemoselectivity in a subsequent chemical reaction. Protecting groups are described, for example, in Greene & Wuts, eds., "Protecting Groups in Organic Synthesis", 2nd ed. New York; John Wiley & Sons, Inc., 1991. For a particular compound and/or a particular chemical reaction, a person skilled in the art knows how to select and implement appropriate protecting groups and synthetic methods. Examples of nitrogen protecting groups include acyl and alkoxycarbonyl groups, such as t-butoxycarbonyl (BOC), and silyl groups, such as [2- (trimethylsilyl)ethoxy]methyl (SEM). Examples of carboxyl protecting groups include (1 - 6C)alkyl groups, such as methyl, ethyl and t-butyl. Examples of alcohol protecting groups include benzyl, trityl, silyl ethers, and the like. [0049] As used herein “leaving group” refers to a molecule or a molecular fragment (e.g., an anion) that is displaced in a chemical reaction as stable species taking with it the bonding electrons. Examples of leaving groups include arylsulfonyloxy group or an alkylsulfonyloxy group, such as a mesylate or a tosylate group. Common anionic leaving groups also include halides such as Cl-, Br-, and I-. Compounds of Formula I [0050] In one aspect the present invention relates to a compound of formula I, or a salt thereof: (I), wherein, R ¹ is selected from the group consisting of hydrogen, C1-10alkyl optionally substituted by one or more R ^a1 , C2-10alkenyl optionally substituted by one or more R ^a1 , C2-6alkynyl optionally substituted by one or more R ^a1 , C6-15aryl optionally substituted by one or more R ^a1 , C6-15aryl(C1-6)alkyl optionally substituted by one or more R ^a1 , C3-11cycloalkyl optionally substituted by one or more R ^a1 , C3-11cycloalkyl(C1-6)alkyl optionally substituted by one or more R ^a1 , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a1 , 4-15 membered heterocycloalkyl(C1-6)alkyl optionally substituted by one or more R ^a1 , 4-15 membered heteroaryl optionally substituted by one or more R ^a1 , and 4-15 membered heteroaryl(C1-6)alkyl optionally substituted by one or more R ^a1 , –C(=O)R ^b , –C(=O)OR ^c , – C(=O)NR ^d R ^e , and –C(O)C(=O)R ^b ; where each R ^a1 is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _{1- 6} haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , – NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O) ₂ R ^b , –NR ^d S(=O) ₂ NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , – OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O) ₂ R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O) ₂ R ^c , – OS(=O) ₂ OR ^c , –S(=O)NR ^d R ^e , –OS(=O) ₂ NR ^d R ^e , and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O- C _1-6 alkyl, C _3-6 cycloalkyl, and 3-7 membered heterocycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl; R ² is selected from the group consisting of hydrogen, C _1-10 alkyl optionally substituted by one or more R ^a2 , C _2-10 alkenyl optionally substituted by one or more R ^a2 , C _2-6 alkynyl optionally substituted by one or more R ^a2 , C _6-15 aryl optionally substituted by one or more R ^a2 , C _6-15 aryl(C _1-6 )alkyl optionally substituted by one or more R ^a2 , C _3-11 cycloalkyl optionally substituted by one or more R ^a2 , C _3-11 cycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a2 , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a2 , 4-15 membered heterocycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a2 , 4-15 membered heteroaryl optionally substituted by one or more R ^a2 , and 4-15 membered heteroaryl(C1-6)alkyl optionally substituted by one or more R ^a2 , –C(=O)R ^b , –C(=O)OR ^c , – C(=O)NR ^d R ^e , and –C(O)C(=O)R ^b ; where each R ^a2 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1- 6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , – NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O)2R ^b , –NR ^d S(=O)2NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , – OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O)2R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O)2R ^c , – OS(=O)2OR ^c , –S(=O)NR ^d R ^e , –OS(=O)2NR ^d R ^e , and –S(=O)2NR ^d R ^e , where said C1-6 alkyl, O- C1-6 alkyl, C3-6 cycloalkyl, and 3-7 membered heterocycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl and O-C1-6 alkyl; or R ¹ is absent and R ² combines with the nitrogen to which it is attached to form an imino group of formula =CR ^w R ^x , an amidine of formula =C(R ^w )(NR ^y R ^z ), or a guanidine of formula =C(NR ^y R ^z )2 where R ^w , R ^x are independently C1-6 alkyl and R ^y and R ^z are independently selected from hydrogen and C1-6 alkyl; or R ¹ and R ² together with the nitrogen atom to which they are attached form a 3-15 membered heterocycloalkyl ring or 4-15 membered heteroaryl ring, each independently and optionally containing one or more further heteroatoms selected from O, N, and S and wherein each ring is independently and optionally substituted with one or more R ^a3 ; where each R ^a3 is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _{1- 6} haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-15 membered heterocycloalkyl, 4-15 membered heteroaryl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , –NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O) ₂ R ^b , –NR ^d S(=O) ₂ NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , –OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O) ₂ R ^c , –S(=O)R ^c , –OS(=O)R ^c , – OS(=O) ₂ R ^c , –OS(=O) ₂ OR ^c , –S(=O)NR ^d R ^e , –OS(=O) ₂ NR ^d R ^e , and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-15 membered heterocycloalkyl, and 4-15 membered heteroaryl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl; R is selected from the group consisting of C _1-10 alkyl optionally substituted by one or more R ^a , C _2-10 alkenyl optionally substituted by one or more R ^a , C _2-6 alkynyl optionally substituted by one or more R ^a , C _6-15 aryl optionally substituted by one or more R ^a , C _6-15 aryl(C _{1- 6} )alkyl optionally substituted by one or more R ^a , C _3-11 cycloalkyl optionally substituted by one or more R ^a , C _3-11 cycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a , 4-15 membered heterocycloalkyl(C1- 6)alkyl optionally substituted by one or more R ^a , 4-15 membered heteroaryl optionally substituted by one or more R ^a , and 4-15 membered heteroaryl(C1-6)alkyl optionally substituted by one or more R ^a ; where each R ^a is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, C6-11 aryl, – C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , – NR ^d C(=O)OR ^c , –NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O)2R ^b , –NR ^d S(=O)2NR ^d R ^e , –OR ^c , –SR ^c , – OC(=O)R ^b , –OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O)2R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O)2R ^c , –OS(=O)2OR ^c , –S(=O)NR ^d R ^e , –OS(=O)2NR ^d R ^e , and –S(=O)2NR ^d R ^e , where said C1-6 alkyl, O- C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl and C6-11 aryl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl; R ³ is selected from the group consisting of H, C1-6 alkyl, CN, –C(=O)R ^f , –C(=O)OR ^g , – C(=O)NR ^h R ^j , –C(O)C(=O)R ^f , –NR ^h R ^j , –NR ^g C(=O)R ^f , –NR ^h C(=O)OR ^g , –NR ^h C(=O)NR ^h R ^j , – NR ^h S(=O) ₂ R ^f , –NR ^h S(=O) ₂ NR ^h R ^j , –OR ^g , –SR ^g , –OC(=O)R ^f , –OC(=O)NR ^h R ^j , –OC(=O)OR ^g , – S(=O) ₂ R ^g , –S(=O)R ^g , –OS(=O)R ^g , –OS(=O) ₂ R ^g , –OS(=O) ₂ OR ^g , –S(=O)NR ^h R ^j , – OS(=O) ₂ NR ^h R ^j , and –S(=O) ₂ NR ^h R ^j , where said C _1-6 alkyl is optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl; R ⁴ is selected from the group consisting of hydrogen, C _1-10 alkyl optionally substituted by one or more R ^a4 , C _2-10 alkenyl optionally substituted by one or more R ^a4 , C _2-6 alkynyl optionally substituted by one or more R ^a4 , C _6-15 aryl optionally substituted by one or more R ^a4 , C _6-15 aryl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , C _3-11 cycloalkyl optionally substituted by one or more R ^a4 , C _3-11 cycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a4 , 4-15 membered heterocycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , 4-15 membered heteroaryl optionally substituted by one or more R ^a4 , and 4-15 membered heteroaryl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , CN, –C(=O)R ^f , –C(=O)OR ^g , – C(=O)NR ^h R ^j , –C(O)C(=O)R ^f , –OR ^g , –SR ^g , –OC(=O)R ^f , –OC(=O)NR ^h R ^j , –OC(=O)OR ^g , – S(=O) ₂ R ^g , –S(=O)R ^g , –OS(=O)R ^g , –OS(=O) ₂ R ^g , –OS(=O) ₂ OR ^g , –S(=O)NR ^h R ^j , – OS(=O) ₂ NR ^h R ^j , and –S(=O) ₂ NR ^h R ^j ; where each R ^a4 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1- 6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , – NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O)2R ^b , –NR ^d S(=O)2NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , – OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O)2R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O)2R ^c , – OS(=O)2OR ^c , –S(=O)NR ^d R ^e , –OS(=O)2NR ^d R ^e , and –S(=O)2NR ^d R ^e , where said C1-6 alkyl, O- C1-6 alkyl, C3-6 cycloalkyl, and 3-7 membered heterocycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl and O-C1-6 alkyl; wherein each R ^b and R ^f are independently selected from hydrogen, hydroxyl, halogen, CN, C1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, C6-15 aryl, C6-15aryl(C1-6)alkyl, C3-11cycloalkyl(C1-6)alkyl, 4-15 membered heterocycloalkyl(C1-6)alkyl, and 4-15 membered heteroaryl(C1-6)alkyl, wherein said C1-6 alkyl, C6-15 aryl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C6- 15aryl(C1-6)alkyl, C3-11cycloalkyl(C1-6)alkyl, 4-15 membered heterocycloalkyl(C1-6)alkyl, and 4- 15 membered heteroaryl(C1-6)alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO2, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl; wherein each R ^c and R ^g are independently selected from hydrogen, hydroxyl, halogen, CN, C _1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl and C _6-15 aryl, wherein said C _1-6 alkyl, C _6-15 aryl, 3-7 membered heterocycloalkyl 5-6 membered heteroaryl and C _3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, nitro, amino, C _1-6 haloalkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl; wherein each R ^d and R ^h are independently selected from hydrogen, hydroxyl, halogen, CN, C _1-6 haloalkyl, C _3-6 cycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl; wherein each R ^e and R ^j are independently selected from hydrogen, hydroxyl, halogen, CN, C _1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, C _6-15 aryl, C _6-15 aryl(C _1-6 )alkyl, C _3-11 cycloalkyl(C _1-6 )alkyl, 4-15 membered heterocycloalkyl(C _1-6 )alkyl, and 4-15 membered heteroaryl(C _1-6 )alkyl, wherein said C _1-6 alkyl, C _6-15 aryl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C _3-6 cycloalkyl, C _{6- 15} aryl(C _1-6 )alkyl, C _3-11 cycloalkyl(C _1-6 )alkyl, 4-15 membered heterocycloalkyl(C _1-6 )alkyl, and 4- 15 membered heteroaryl(C _1-6 )alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO ₂ , C _1-6 haloalkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl; or wherein R ^d and R ^e , when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more for heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more R ^k ; wherein R ^h and R ^j , when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more for heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more R ^k ; where R ^k is selected from hydrogen, =O, halogen, CN, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl and O-C1-6 alkyl; with the provisos that: (i) when R is methyl, ethyl or butyl then R ³ and R ⁴ cannot both be methyl; and (ii) when R is optionally substituted phenyl then R ³ and R ⁴ cannot both be -SO2CF3. R [0051] In one embodiment, R is selected from the group consisting of C _1-10 alkyl optionally substituted by one or more R ^a , C2-10alkenyl optionally substituted by one or more R ^a , C2- 6alkynyl optionally substituted by one or more R ^a , C6-15aryl optionally substituted by one or more R ^a , C6-15aryl(C1-6)alkyl optionally substituted by one or more R ^a , C3-11cycloalkyl optionally substituted by one or more R ^a , C _3-11 cycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a , 4-15 membered heterocycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a , 4-15 membered heteroaryl optionally substituted by one or more R ^a , and 4-15 membered heteroaryl(C _1-6 )alkyl optionally substituted by one or more R ^a ; [0052] In another embodiment, R is selected from the group consisting of C _1-6 alkyl optionally substituted by one or more R ^a , C _6-12 aryl optionally substituted by one or more R ^a , C _3-7 cycloalkyl optionally substituted by one or more R ^a , 5-12 membered heterocycloalkyl optionally substituted by one or more R ^a , and 5-12 membered heteroaryl optionally substituted by one or more R ^a . [0053] In another embodiment, R is selected from the group consisting of C _6-12 aryl optionally substituted by one or more R ^a , 5-12 membered heterocycloalkyl optionally substituted by one or more R ^a , and 5-12 membered heteroaryl optionally substituted by one or more R ^a . [0054] In another embodiment, R is selected from the group consisting of phenyl optionally substituted by one or more R ^a , 5-10 membered heterocycloalkyl optionally substituted by one or more R ^a , and 5-10 membered heteroaryl optionally substituted by one or more R ^a . [0055] In another embodiment, R is selected from the group consisting of phenyl optionally substituted by one or more R ^a , 5-10 membered heterocycloalkyl optionally substituted by one or more R ^a , and 5-10 membered heteroaryl optionally substituted by one or more R ^a . [0056] In another embodiment, R is selected from the group consisting of phenyl optionally substituted by one or more R ^a , 5-7 membered heterocycloalkyl optionally substituted by one or more R ^a , and 5-6 membered heteroaryl optionally substituted by one or more R ^a . [0057] In one embodiment, R ^a is independently selected from hydroxyl, =O, halogen, CN, C1- 6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , – NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , –NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O)2R ^b , –NR ^d S(=O)2NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , –OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O)2R ^c , –S(=O)R ^c , –OS(=O)R ^c , – OS(=O) ₂ R ^c , –OS(=O) ₂ OR ^c , –S(=O)NR ^d R ^e , –OS(=O) ₂ NR ^d R ^e , and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [0058] In another embodiment, R ^a is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, –C(=O)R ^b , –C(=O)NR ^d R ^e , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d S(=O) ₂ R ^b , – OR ^c , –SR ^c , –OC(=O)R ^b , –S(=O) ₂ R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O) ₂ R ^c , –OS(=O) ₂ OR ^c , – S(=O)NR ^d R ^e , –OS(=O) ₂ NR ^d R ^e , and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [0059] In another embodiment, R ^a is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, –C(=O)R ^b , –C(=O)NR ^d R ^e , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d S(=O)2R ^b , – OR ^c , –SR ^c , –OC(=O)R ^b , –S(=O) ₂ R ^c , –S(=O)R ^c , –OS(=O)R ^c , –S(=O)NR ^d R ^e and – S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. [0060] In another embodiment, R ^a is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, –NR ^d R ^e , –OR ^c , –SR ^c , where said C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. [0061] In another embodiment, R ^a is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, where said C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. [0062] In another embodiment, R ^a is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, where said C _1-6 alkyl and O-C _1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [0063] In another embodiment, R ^a is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, where said C _1-6 alkyl and O-C _1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [0064] Suitably, R is selected from the group consisting of phenyl optionally substituted by one or more R ^a , 5-7 membered heterocycloalkyl optionally substituted by one or more R ^a , and 5-6 membered heteroaryl optionally substituted by one or more R ^a , wherein R ^a is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, where said C1-6 alkyl and O-C1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. R1 [0065] In one embodiment, R ¹ is selected from the group consisting of hydrogen, C1-10alkyl optionally substituted by one or more R ^a1 , C2-10alkenyl optionally substituted by one or more R ^a1 , C2-6alkynyl optionally substituted by one or more R ^a1 , C6-15aryl optionally substituted by one or more R ^a1 , C6-15aryl(C1-6)alkyl optionally substituted by one or more R ^a1 , C3-11cycloalkyl optionally substituted by one or more R ^a1 , C3-11cycloalkyl(C1-6)alkyl optionally substituted by one or more R ^a1 , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a1 , 4-15 membered heterocycloalkyl(C1-6)alkyl optionally substituted by one or more R ^a1 , 4-15 membered heteroaryl optionally substituted by one or more R ^a1 , and 4-15 membered heteroaryl(C1-6)alkyl optionally substituted by one or more R ^a1 , –C(=O)R ^b , –C(=O)OR ^c , – C(=O)NR ^d R ^e , and –C(O)C(=O)R ^b . [0066] In another embodiment, R ¹ is selected from the group consisting of hydrogen, C _1-6 alkyl optionally substituted by one or more R ^a1 , C _2-6 alkenyl optionally substituted by one or more R ^a1 , C2-6alkynyl optionally substituted by one or more R ^a1 , C6-12aryl optionally substituted by one or more R ^a1 , C6-12aryl(C1-3)alkyl optionally substituted by one or more R ^a1 , C3-10cycloalkyl optionally substituted by one or more R ^a1 , C3-10cycloalkyl(C1-3)alkyl optionally substituted by one or more R ^a1 , 3-12 membered heterocycloalkyl optionally substituted by one or more R ^a1 , 4-12 membered heterocycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a1 , 4-12 membered heteroaryl optionally substituted by one or more R ^a1 , and 4-12 membered heteroaryl(C _1-3 )alkyl optionally substituted by one or more R ^a1 , –C(=O)R ^b , –C(=O)OR ^c , – C(=O)NR ^d R ^e , and –C(O)C(=O)R ^b . [0067] In another embodiment, R ¹ is selected from the group consisting of hydrogen, C _1-6 alkyl optionally substituted by one or more R ^a1 , C _2-6 alkenyl optionally substituted by one or more R ^a1 , C _2-6 alkynyl optionally substituted by one or more R ^a1 , –C(=O)R ^b , –C(=O)OR ^c , – C(=O)NR ^d R ^e , and –C(O)C(=O)R ^b . [0068] In another embodiment, R ¹ is selected from the group consisting of hydrogen, C _1-6 alkyl optionally substituted by one or more R ^a1 , –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , and – C(O)C(=O)R ^b . [0069] In another embodiment, R ¹ is selected from the group consisting of hydrogen, C1-6alkyl optionally substituted by one or more R ^a1 , –C(=O)R ^b , and –C(=O)NR ^d R ^e . [0070] In another embodiment, R ¹ is selected from the group consisting of hydrogen, C _1-6 alkyl optionally substituted by one or more R ^a1 , and –C(=O)NR ^d R ^e . [0071] In another embodiment, R ¹ is hydrogen or C1-6alkyl optionally substituted by one or more R ^a1 . [0072] In one embodiment, R ^a1 is independently selected from hydroxyl, =O, halogen, CN, C1- 6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , – NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , –NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O)2R ^b , –NR ^d S(=O)2NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , –OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O)2R ^c , –S(=O)R ^c , –OS(=O)R ^c , – OS(=O)2R ^c , –OS(=O)2OR ^c , –S(=O)NR ^d R ^e , –OS(=O)2NR ^d R ^e , and –S(=O)2NR ^d R ^e , where said C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [0073] In another embodiment, R ^a1 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, –C(=O)R ^b , –C(=O)NR ^d R ^e , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d S(=O)2R ^b , – OR ^c , –SR ^c , –OC(=O)R ^b , –S(=O) ₂ R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O) ₂ R ^c , –OS(=O) ₂ OR ^c , – S(=O)NR ^d R ^e , –OS(=O) ₂ NR ^d R ^e , and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [0074] In another embodiment, R ^a1 is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, –C(=O)R ^b , –C(=O)NR ^d R ^e , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d S(=O) ₂ R ^b , – OR ^c , –SR ^c , –OC(=O)R ^b , –S(=O) ₂ R ^c , –S(=O)R ^c , –OS(=O)R ^c , –S(=O)NR ^d R ^e and – S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [0075] In another embodiment, R ^a1 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, –NR ^d R ^e , –OR ^c , –SR ^c , where said C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. [0076] In another embodiment, R ^a1 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, where said C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. [0077] In another embodiment, R ^a1 is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, where said C _1-6 alkyl and O-C _1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. [0078] In another embodiment, R ^a1 is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, where said C _1-6 alkyl and O-C _1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [0079] In another embodiment, R ^a1 is independently selected from hydroxyl, C _1-6 haloalkyl, C _{1- 6} haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, where said C _1-6 alkyl and O-C _1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. R2 [0080] In one embodiment, R ² is selected from the group consisting of hydrogen, C _1-6 alkyl optionally substituted by one or more R ^a2 , C _2-6 alkenyl optionally substituted by one or more R ^a2 , C _2-6 alkynyl optionally substituted by one or more R ^a2 , C _6-12 aryl optionally substituted by one or more R ^a2 , C _6-12 aryl(C _1-3 )alkyl optionally substituted by one or more R ^a2 , C _3-7 cycloalkyl optionally substituted by one or more R ^a2 , C _3-7 cycloalkyl(C _1-3 )alkyl optionally substituted by one or more R ^a2 , 3-12 membered heterocycloalkyl optionally substituted by one or more R ^a2 , 4-12 membered heterocycloalkyl(C _1-3 )alkyl optionally substituted by one or more R ^a2 , 4-12 membered heteroaryl optionally substituted by one or more R ^a2 , and 4-12 membered heteroaryl(C1-3)alkyl optionally substituted by one or more R ^a2 , –C(=O)R ^b , –C(=O)OR ^c , – C(=O)NR ^d R ^e , and –C(O)C(=O)R ^b . [0081] In one embodiment, R ² is selected from the group consisting of hydrogen, C1-6alkyl optionally substituted by one or more R ^a2 , C2-6alkenyl optionally substituted by one or more R ^a2 , phenyl optionally substituted by one or more R ^a2 , phenyl(C1-3)alkyl optionally substituted by one or more R ^a2 , C3-7cycloalkyl optionally substituted by one or more R ^a2 , C3-7cycloalkyl(C1- 3)alkyl optionally substituted by one or more R ^a2 , 3-12 membered heterocycloalkyl optionally substituted by one or more R ^a2 , 4-12 membered heterocycloalkyl(C1-3)alkyl optionally substituted by one or more R ^a2 , 4-12 membered heteroaryl optionally substituted by one or more R ^a2 , and 4-12 membered heteroaryl(C1-3)alkyl optionally substituted by one or more R ^a2 , –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , and –C(O)C(=O)R ^b . [0082] In one embodiment, R ² is selected from the group consisting of hydrogen, C _1-6 alkyl optionally substituted by one or more R ^a2 , C _2-6 alkenyl optionally substituted by one or more R ^a2 , C _2-6 alkynyl optionally substituted by one or more R ^a2 , C _6-11 aryl optionally substituted by one or more R ^a2 , C3-7cycloalkyl optionally substituted by one or more R ^a2 , 5-12 membered heterocycloalkyl optionally substituted by one or more R ^a2 , 5-12 membered heteroaryl optionally substituted by one or more R ^a2 , –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , and – C(O)C(=O)R ^b . [0083] In one embodiment, R ² is selected from the group consisting of hydrogen, C _1-6 alkyl optionally substituted by one or more R ^a2 , C _2-6 alkenyl optionally substituted by one or more R ^a2 , phenyl optionally substituted by one or more R ^a2 , C _3-7 cycloalkyl optionally substituted by one or more R ^a2 , 4-7 membered heterocycloalkyl optionally substituted by one or more R ^a2 , 4- 12 membered heteroaryl optionally substituted by one or more R ^a2 , –C(=O)R ^b , –C(=O)OR ^c , – C(=O)NR ^d R ^e , and –C(O)C(=O)R ^b . [0084] In one embodiment, R ² is selected from the group consisting of hydrogen, C _1-6 alkyl optionally substituted by one or more R ^a2 , C _2-6 alkenyl optionally substituted by one or more R ^a2 , phenyl optionally substituted by one or more R ^a2 , C _3-7 cycloalkyl optionally substituted by one or more R ^a2 , 4-7 membered heterocycloalkyl optionally substituted by one or more R ^a2 , 5- 6 membered heteroaryl optionally substituted by one or more R ^a2 , –C(=O)R ^b , and – C(=O)NR ^d R ^e . [0085] In one embodiment, R ² is selected from the group consisting of hydrogen, C1-6alkyl optionally substituted by one or more R ^a2 , C2-6alkenyl optionally substituted by one or more R ^a2 , phenyl optionally substituted by one or more R ^a2 , C _3-7 cycloalkyl optionally substituted by one or more R ^a2 , 4-7 membered heterocycloalkyl optionally substituted by one or more R ^a2 , and 5-6 membered heteroaryl optionally substituted by one or more R ^a2 . [0086] In one embodiment, R ² is hydrogen or C1-6alkyl optionally substituted by one or more R ^a2 . [0087] In one embodiment, R ^a2 is independently selected from hydroxyl, =O, halogen, CN, C1- 6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , – NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , –NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O)2R ^b , –NR ^d S(=O)2NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , –OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O)2R ^c , –S(=O)R ^c , –OS(=O)R ^c , – OS(=O)2R ^c , –OS(=O)2OR ^c , –S(=O)NR ^d R ^e , –OS(=O)2NR ^d R ^e , and –S(=O)2NR ^d R ^e , where said C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [0088] In another embodiment, R ^a2 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, –C(=O)R ^b , –C(=O)NR ^d R ^e , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d S(=O)2R ^b , – OR ^c , –SR ^c , –OC(=O)R ^b , –S(=O) ₂ R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O) ₂ R ^c , –OS(=O) ₂ OR ^c , – S(=O)NR ^d R ^e , –OS(=O) ₂ NR ^d R ^e , and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [0089] In another embodiment, R ^a2 is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, –C(=O)R ^b , –C(=O)NR ^d R ^e , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d S(=O) ₂ R ^b , – OR ^c , –SR ^c , –OC(=O)R ^b , –S(=O) ₂ R ^c , –S(=O)R ^c , –OS(=O)R ^c , –S(=O)NR ^d R ^e and – S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [0090] In another embodiment, R ^a2 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, –NR ^d R ^e , –OR ^c , –SR ^c , where said C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. [0091] In another embodiment, R ^a2 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, where said C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. [0092] In another embodiment, R ^a2 is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, where said C _1-6 alkyl and O-C _1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. [0093] In another embodiment, R ^a2 is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, where said C _1-6 alkyl and O-C _1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [0094] In another embodiment, R ^a2 is independently selected from hydroxyl, C _1-6 haloalkyl, C _{1- 6} haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, where said C _1-6 alkyl and O-C _1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. R1 and R2 [0095] In one embodiment, R ¹ is absent and R ² combines with the nitrogen to which it is attached to form an imino group of formula =CR ^w R ^x , an amidine of formula =C(R ^w )(NR ^y R ^z ), or a guanidine of formula =C(NR ^y R ^z ) ₂ , where R ^w , R ^x are independently C _1-6 alkyl and R ^y and R ^z are independently selected from hydrogen and C _1-6 alkyl. [0096] In another embodiment, R ¹ is absent and R ² combines with the nitrogen to which it is attached to form an amidine of formula =C(R ^w )(NR ^y R ^z ), or a guanidine of formula =C(NR ^y R ^z ) ₂ , where R ^w , R ^x are independently C1-3 alkyl and R ^y and R ^z are independently selected from hydrogen and C1-3 alkyl. [0097] In one embodiment, R ¹ and R ² together with the nitrogen atom to which they are attached form a 3-12 membered heterocycloalkyl ring or 4-12 membered heteroaryl ring, each independently and optionally containing one or more further heteroatoms selected from O, N, and S and wherein each ring is independently and optionally substituted with one or more R ^a3 . [0098] In one embodiment, R ¹ and R ² together with the nitrogen atom to which they are attached form a 3-7 membered heterocycloalkyl ring or 5-12 membered heteroaryl ring, each independently and optionally containing one or more further heteroatoms selected from O, N, and S and wherein each ring is independently and optionally substituted with one or more R ^a3 . [0099] In one embodiment, R ¹ and R ² together with the nitrogen atom to which they are attached form a 5-7 membered heterocycloalkyl ring or 5-12 membered heteroaryl ring, each independently and optionally containing one or more further heteroatoms selected from O, N, and S and wherein each ring is independently and optionally substituted with one or more R ^a3 . [00100] In one embodiment, R ¹ and R ² together with the nitrogen atom to which they are attached form a 5-7 membered heterocycloalkyl ring or 5-10 membered heteroaryl ring, each independently and optionally containing one or more further heteroatoms selected from O, N, and S and wherein each ring is independently and optionally substituted with one or more R ^a3 . [00101] In one embodiment, R ¹ and R ² together with the nitrogen atom to which they are attached form a 5-7 membered heterocycloalkyl ring or 5-6 membered heteroaryl ring, each independently and optionally containing one or more further heteroatoms selected from O, N, and S and wherein each ring is independently and optionally substituted with one or more R ^a3 . [00102] In one embodiment, R ^a3 is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , – C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , –NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O) ₂ R ^b , – NR ^d S(=O) ₂ NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , –OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O) ₂ R ^c , – S(=O)R ^c , –OS(=O)R ^c , –OS(=O) ₂ R ^c , –OS(=O) ₂ OR ^c , –S(=O)NR ^d R ^e , –OS(=O) ₂ NR ^d R ^e , and – S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. [00103] In another embodiment, R ^a3 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, –C(=O)R ^b , –C(=O)NR ^d R ^e , – NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d S(=O)2R ^b , –OR ^c , –SR ^c , –OC(=O)R ^b , –S(=O)2R ^c , –S(=O)R ^c , – OS(=O)R ^c , –OS(=O)2R ^c , –OS(=O)2OR ^c , –S(=O)NR ^d R ^e , –OS(=O)2NR ^d R ^e , and –S(=O)2NR ^d R ^e , where said C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1- 6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. [00104] In another embodiment, R ^a3 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, –C(=O)R ^b , –C(=O)NR ^d R ^e , – NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d S(=O)2R ^b , –OR ^c , –SR ^c , –OC(=O)R ^b , –S(=O)2R ^c , –S(=O)R ^c , – OS(=O)R ^c , –S(=O)NR ^d R ^e and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [00105] In another embodiment, R ^a3 is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, –NR ^d R ^e , –OR ^c , –SR ^c , where said C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [00106] In another embodiment, R ^a3 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl, where said C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. [00107] In another embodiment, R ^a3 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, where said C1-6 alkyl and O-C1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. [00108] In another embodiment, R ^a3 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, where said C1-6 alkyl and O-C1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. [00109] In another embodiment, R ^a3 is independently selected from hydroxyl, =O, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, where said C1-6 alkyl and O-C1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. [00110] In one embodiment, R ¹ and R ² together with the nitrogen atom to which they are attached form a 5-7 membered heterocycloalkyl ring or 5-6 membered heteroaryl ring, each independently and optionally containing one or more further heteroatoms selected from O, N, and S and wherein each ring is independently and optionally substituted with one or more substitutents selected from hydroxyl, =O, C _1-6 haloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, where said C _1-6 alkyl is optionally substituted with one or more groups selected from hydroxyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [00111] In one embodiment, R ¹ and R ² are independently selected from hydrogen or C _1-6 alkyl optionally substituted by one or more R ^a1 or R ^a2 respectively; or R ¹ and R ² together with the nitrogen atom to which they are attached, form a 3-15 membered heterocycloalkyl ring or 4-15 membered heteroaryl ring, each independently and optionally containing one or more further heteroatoms selected from O, N, and S and wherein each ring is independently and optionally substituted with one or more R ^a3 . [00112] In one embodiment, R ¹ and R ² are independently selected from hydrogen or C _1-6 alkyl optionally substituted by one or more R ^a1 or R ^a2 respectively; or, R ¹ and R ² together with the nitrogen atom to which they are attached, form a 4-12 membered heterocycloalkyl ring or 5-12 membered heteroaryl ring, each independently and optionally containing one or more further heteroatoms selected from O, N, and S and wherein each ring is independently and optionally substituted with one or more R ^a3 . [00113] In one embodiment, R ¹ and R ² are independently selected from hydrogen or C1-6alkyl optionally substituted by one or more R ^a1 or R ^a2 respectively; or, R ¹ and R ² together with the nitrogen atom to which they are attached, form a 5-10 membered heterocycloalkyl ring or 5-10 membered heteroaryl ring, each independently and optionally containing one or more further heteroatoms selected from O, N, and S and wherein each ring is independently and optionally substituted with one or more R ^a3 . [00114] In one embodiment, R ¹ and R ² are independently selected from hydrogen or C1-3alkyl optionally substituted by one or more R ^a1 or R ^a2 respectively; or, R ¹ and R ² together with the nitrogen atom to which they are attached, form a 5-7 membered heterocycloalkyl ring or 5-6 membered heteroaryl ring, each independently and optionally containing one or more further heteroatoms selected from O, N, and S and wherein each ring is independently and optionally substituted with one or more R ^a3 . [00115] In one embodiment, R ¹ is hydrogen and R ² is hydrogen. R3 [00116] In one embodiment, R ³ is selected from the group consisting of H, C _1-6 alkyl, CN, –C(=O)R ^f , –C(=O)NR ^h R ^j , –OR ^g , –SR ^g , –OC(=O)R ^f , –OC(=O)NR ^h R ^j , –OC(=O)OR ^g , – S(=O) ₂ R ^g , –S(=O)R ^g , –OS(=O)R ^g , –OS(=O) ₂ R ^g , –OS(=O) ₂ OR ^g , –S(=O)NR ^h R ^j , – OS(=O) ₂ NR ^h R ^j , and –S(=O) ₂ NR ^h R ^j , where said C _1-6 alkyl is optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl. [00117] In one embodiment, R ³ is selected from the group consisting of H, C _1-6 alkyl, CN, –C(=O)R ^f , –C(=O)NR ^h R ^j , –OR ^g , –OC(=O)R ^f , –OC(=O)NR ^h R ^j , –OC(=O)OR ^g , where said C _1-6 alkyl is optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl. [00118] In one embodiment, R ³ is selected from the group consisting of H, C _1-6 alkyl, CN, –C(=O)R ^f , –C(=O)OR ^g , –C(=O)NR ^h R ^j , –S(=O) ₂ R ^g , –S(=O)R ^g , ––S(=O)NR ^h R ^j , and – S(=O) ₂ NR ^h R ^j , where said C _1-6 alkyl is optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl and O-C1-6 alkyl. [00119] In one embodiment, R ³ is selected from the group consisting of H, C1-6 alkyl, CN, –C(=O)R ^f and –C(=O)NR ^h R ^j , where said C1-6 alkyl is optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl and O-C1-6 alkyl. [00120] In one embodiment, R ³ is selected from the group consisting of H, C1-3 alkyl, CN, –C(=O)R ^f and –C(=O)NR ^h R ^j , where said C1-3 alkyl is optionally substituted with one or more groups selected from hydroxyl, CN, C1-3 haloalkyl, C1-3 haloalkoxy, C3-6 cycloalkyl, and O-C _1-3 alkyl. R4 [00121] In one embodiment, R ⁴ is selected from the group consisting of hydrogen, C _{1- 10} alkyl optionally substituted by one or more R ^a4 , C _2-10 alkenyl optionally substituted by one or more R ^a4 , C _2-6 alkynyl optionally substituted by one or more R ^a4 , C _6-15 aryl optionally substituted by one or more R ^a4 , C _6-15 aryl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , C _{3- 11} cycloalkyl optionally substituted by one or more R ^a4 , C _3-11 cycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a4 , 4-15 membered heterocycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , 4-15 membered heteroaryl optionally substituted by one or more R ^a4 , and 4-15 membered heteroaryl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , CN, –C(=O)R ^f , –C(=O)OR ^g , – C(=O)NR ^h R ^j , –C(O)C(=O)R ^f , –OR ^g , –SR ^g , –S(=O) ₂ R ^g , –S(=O)R ^g , –OS(=O)R ^g , –OS(=O) ₂ R ^g , – OS(=O) ₂ OR ^g , –S(=O)NR ^h R ^j , –OS(=O) ₂ NR ^h R ^j , and –S(=O) ₂ NR ^h R ^j . [00122] In one embodiment, R ⁴ is selected from the group consisting of hydrogen, C _{1- 6} alkyl optionally substituted by one or more R ^a4 , C _2-6 alkenyl optionally substituted by one or more R ^a4 , C _2-6 alkynyl optionally substituted by one or more R ^a4 , C _6-11 aryl optionally substituted by one or more R ^a4 , C _6-11 aryl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , C _3-7 cycloalkyl optionally substituted by one or more R ^a4 , C3-7cycloalkyl(C1-6)alkyl optionally substituted by one or more R ^a4 , 5-12 membered heterocycloalkyl optionally substituted by one or more R ^a4 , 5-12 membered heterocycloalkyl(C1-6)alkyl optionally substituted by one or more R ^a4 , 5-12 membered heteroaryl optionally substituted by one or more R ^a4 , and 5-12 membered heteroaryl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , –C(=O)R ^f , –C(=O)OR ^g , – C(=O)NR ^h R ^j , –OR ^g , –SR ^g , –S(=O) ₂ R ^g , –S(=O)R ^g , –S(=O)NR ^h R ^j , and –S(=O) ₂ NR ^h R ^j . [00123] In one embodiment, R ⁴ is selected from the group consisting of hydrogen, C1- 10alkyl optionally substituted by one or more R ^a4 , C2-10alkenyl optionally substituted by one or more R ^a4 , C2-6alkynyl optionally substituted by one or more R ^a4 , C6-12aryl optionally substituted by one or more R ^a4 , C6-12aryl(C1-3)alkyl optionally substituted by one or more R ^a4 , C3-7cycloalkyl optionally substituted by one or more R ^a4 , C3-7cycloalkyl(C1-3)alkyl optionally substituted by one or more R ^a4 , 3-12 membered heterocycloalkyl optionally substituted by one or more R ^a4 , 4-12 membered heterocycloalkyl(C1-6)alkyl optionally substituted by one or more R ^a4 , 4-12 membered heteroaryl optionally substituted by one or more R ^a4 , and 4-12 membered heteroaryl(C1-6)alkyl optionally substituted by one or more R ^a4 , CN, –C(=O)R ^f , –C(=O)OR ^g , – C(=O)NR ^h R ^j , –C(O)C(=O)R ^f , –OR ^g , –SR ^g , –S(=O)2R ^g , –S(=O)R ^g , –OS(=O)R ^g , –OS(=O)2R ^g , – OS(=O)2OR ^g , –S(=O)NR ^h R ^j , –OS(=O)2NR ^h R ^j , and –S(=O)2NR ^h R ^j . [00124] In one embodiment, R ⁴ is selected from the group consisting of hydrogen, C _{1- 10} alkyl optionally substituted by one or more R ^a4 , C _2-10 alkenyl optionally substituted by one or more R ^a4 , C2-6alkynyl optionally substituted by one or more R ^a4 , C6-12aryl optionally substituted by one or more R ^a4 , C6-12aryl(C1-3)alkyl optionally substituted by one or more R ^a4 , C3-7cycloalkyl optionally substituted by one or more R ^a4 , C3-7cycloalkyl(C1-3)alkyl optionally substituted by one or more R ^a4 , 3-12 membered heterocycloalkyl optionally substituted by one or more R ^a4 , 4-12 membered heterocycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , 4-12 membered heteroaryl optionally substituted by one or more R ^a4 , and 4-12 membered heteroaryl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , CN, –C(=O)R ^f , –C(=O)OR ^g , – C(=O)NR ^h R ^j , –C(O)C(=O)R ^f , –OR ^g , –SR ^g , –S(=O) ₂ R ^g , –S(=O)R ^g , –S(=O)NR ^h R ^j , and – S(=O) ₂ NR ^h R ^j . [00125] In one embodiment, R ⁴ is selected from the group consisting of hydrogen, C _{1- 10} alkyl optionally substituted by one or more R ^a4 , C _2-10 alkenyl optionally substituted by one or more R ^a4 , C _2-6 alkynyl optionally substituted by one or more R ^a4 , C _6-12 aryl optionally substituted by one or more R ^a4 , C _6-12 aryl(C _1-3 )alkyl optionally substituted by one or more R ^a4 , C _3-7 cycloalkyl optionally substituted by one or more R ^a4 , C _3-7 cycloalkyl(C _1-3 )alkyl optionally substituted by one or more R ^a4 , 3-12 membered heterocycloalkyl optionally substituted by one or more R ^a4 , 4-12 membered heterocycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , 4-12 membered heteroaryl optionally substituted by one or more R ^a4 , and 4-12 membered heteroaryl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , CN, –C(=O)R ^f , –C(=O)OR ^g , – C(=O)NR ^h R ^j , –OR ^g , –SR ^g , –S(=O)2R ^g , –S(=O)R ^g , –S(=O)NR ^h R ^j , and –S(=O)2NR ^h R ^j . [00126] In one embodiment, R ⁴ is selected from the group consisting of hydrogen, C1- 6alkyl optionally substituted by one or more R ^a4 , C2-6alkenyl optionally substituted by one or more R ^a4 , C2-6alkynyl optionally substituted by one or more R ^a4 , phenyl optionally substituted by one or more R ^a4 , phenyl(C1-3)alkyl optionally substituted by one or more R ^a4 , C3-7cycloalkyl optionally substituted by one or more R ^a4 , C3-7cycloalkyl(C1-3)alkyl optionally substituted by one or more R ^a4 , 5-10 membered heterocycloalkyl optionally substituted by one or more R ^a4 , 5-10 membered heterocycloalkyl(C1-6)alkyl optionally substituted by one or more R ^a4 , 5-10 membered heteroaryl optionally substituted by one or more R ^a4 , and 5-10 membered heteroaryl(C1-6)alkyl optionally substituted by one or more R ^a4 , CN, –C(=O)R ^f , –C(=O)OR ^g , – C(=O)NR ^h R ^j , –OR ^g , –SR ^g , –S(=O)2R ^g , –S(=O)R ^g , –S(=O)NR ^h R ^j , and –S(=O)2NR ^h R ^j . [00127] In one embodiment, R ⁴ is selected from the group consisting of hydrogen, C1- 6alkyl optionally substituted by one or more R ^a4 , C2-6alkenyl optionally substituted by one or more R ^a4 , C _2-6 alkynyl optionally substituted by one or more R ^a4 , phenyl optionally substituted by one or more R ^a4 , phenyl(C _1-3 )alkyl optionally substituted by one or more R ^a4 , 5-10 membered heteroaryl optionally substituted by one or more R ^a4 , and 5-10 membered heteroaryl(C1-6)alkyl optionally substituted by one or more R ^a4 , CN, –C(=O)R ^f , –C(=O)OR ^g , – C(=O)NR ^h R ^j , –OR ^g , and –SR ^g . [00128] In one embodiment, R ⁴ is selected from the group consisting of hydrogen, C _{1- 6} alkyl optionally substituted by one or more R ^a4 , C _2-6 alkenyl optionally substituted by one or more R ^a4 , C _2-6 alkynyl optionally substituted by one or more R ^a4 , phenyl optionally substituted by one or more R ^a4 , phenyl(C _1-3 )alkyl optionally substituted by one or more R ^a4 , 5-10 membered heteroaryl optionally substituted by one or more R ^a4 , and CN, –C(=O)R ^f , – C(=O)OR ^g , –C(=O)NR ^h R ^j , –OR ^g , and –SR ^g . [00129] In one embodiment, R ⁴ is selected from the group consisting of hydrogen, C _{1- 6} alkyl optionally substituted by one or more R ^a4 , C _2-6 alkenyl optionally substituted by one or more R ^a4 , C _2-6 alkynyl optionally substituted by one or more R ^a4 , phenyl optionally substituted by one or more R ^a4, , phenyl(C _1-3 )alkyl optionally substituted by one or more R ^a4 , CN, –C(=O)R ^f , –C(=O)OR ^g , –C(=O)NR ^h R ^j , –OR ^g , and –SR ^g . [00130] In one embodiment, R ⁴ is selected from the group consisting of hydrogen, C _1- 6alkyl optionally substituted by one or more R ^a4 , C2-6alkynyl optionally substituted by one or more R ^a4 , phenyl optionally substituted by one or more R ^a4, , benzyl optionally substituted by one or more R ^a4, , –C(=O)R ^f , –C(=O)OR ^g , –C(=O)NR ^h R ^j and –SR ^g . [00131] In one embodiment, R ⁴ is selected from the group consisting of hydrogen, C _1- 6alkyl optionally substituted by one or more R ^a4 , C2-6alkynyl optionally substituted by one or more R ^a4 , phenyl optionally substituted by one or more R ^a4, , benzyl optionally substituted by one or more R ^a4, , –C(=O)R ^f , –C(=O)OR ^g , –C(=O)NR ^h R ^j and –SR ^g . [00132] In one embodiment, R ^a4 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , – C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , –NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O)2R ^b , – NR ^d S(=O)2NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , –OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O)2R ^c , – S(=O)R ^c , –OS(=O)R ^c , –OS(=O)2R ^c , –OS(=O)2OR ^c , –S(=O)NR ^d R ^e , –OS(=O)2NR ^d R ^e , and – S(=O)2NR ^d R ^e , where said C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [00133] In another embodiment, R ^a4 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, –C(=O)R ^b , –C(=O)NR ^d R ^e , – NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d S(=O) ₂ R ^b , –OR ^c , –SR ^c , –OC(=O)R ^b , –S(=O) ₂ R ^c , –S(=O)R ^c , – OS(=O)R ^c , –OS(=O) ₂ R ^c , –OS(=O) ₂ OR ^c , –S(=O)NR ^d R ^e , –OS(=O) ₂ NR ^d R ^e , and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _{1- 6} alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [00134] In another embodiment, R ^a4 is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, –C(=O)R ^b , –C(=O)NR ^d R ^e , – NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d S(=O) ₂ R ^b , –OR ^c , –SR ^c , –OC(=O)R ^b , –S(=O) ₂ R ^c , –S(=O)R ^c , – OS(=O)R ^c , –S(=O)NR ^d R ^e and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. [00135] In another embodiment, R ^a4 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, –NR ^d R ^e , –OR ^c , –SR ^c , where said C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. [00136] In another embodiment, R ^a4 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl, where said C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [00137] In another embodiment, R ^a4 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, where said C1-6 alkyl and O-C _1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [00138] In another embodiment, R ^a4 is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, where said C _1-6 alkyl and O-C _1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [00139] In another embodiment, R ^a4 is independently selected from hydroxyl, =O, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, where said C _1-6 alkyl and O-C _1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [00140] In one embodiment, R ^b and R ^f are independently selected from hydrogen, CN, 3-7 membered heterocycloalkyl, 5-15 membered heteroaryl, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, C _6-15 aryl, C _6-15 aryl(C _1-6 )alkyl, C _3-11 cycloalkyl(C _1-6 )alkyl, 4-15 membered heterocycloalkyl(C _1-6 )alkyl, and 4-15 membered heteroaryl(C _1-6 )alkyl, wherein said C _1-6 alkyl, C _6-15 aryl, 3-7 membered heterocycloalkyl, 5-15 membered heteroaryl, C _3-6 cycloalkyl, C _{6- 15} aryl(C _1-6 )alkyl, C _3-11 cycloalkyl(C _1-6 )alkyl, 4-15 membered heterocycloalkyl(C _1-6 )alkyl, and 4- 15 membered heteroaryl(C1-6)alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO2, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. [00141] In another embodiment, R ^b and R ^f are independently selected from hydrogen, CN, 3-7 membered heterocycloalkyl, 5-12 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, O- C1-6 alkyl, C6-12 aryl, C6-12aryl(C1-3)alkyl, C3-11cycloalkyl(C1-3)alkyl, 4-12 membered heterocycloalkyl(C1-3)alkyl, and 4-12 membered heteroaryl(C1-3)alkyl, wherein said C1-6 alkyl, C6-12 aryl, 3-7 membered heterocycloalkyl, 5-12 membered heteroaryl, C3-6 cycloalkyl, C6- 12aryl(C1-3)alkyl, C3-11cycloalkyl(C1-3)alkyl, 4-12 membered heterocycloalkyl(C1-3)alkyl, and 4- 12 membered heteroaryl(C1-3)alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO2, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [00142] In another embodiment, R ^b and R ^f are independently selected from hydrogen, 3-7 membered heterocycloalkyl, 5-12 membered heteroaryl, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, C _6-12 aryl, C _6-12 aryl(C _1-3 )alkyl, C _3-11 cycloalkyl(C _1-3 )alkyl, 4-12 membered heterocycloalkyl(C _1-3 )alkyl, and 4-12 membered heteroaryl(C _1-3 )alkyl, wherein said C _1-6 alkyl, C _6-12 aryl, 3-7 membered heterocycloalkyl, 5-12 membered heteroaryl, C _3-6 cycloalkyl, C _{6- 12} aryl(C _1-3 )alkyl, C _3-11 cycloalkyl(C _1-3 )alkyl, 4-12 membered heterocycloalkyl(C _1-3 )alkyl, and 4- 12 membered heteroaryl(C _1-3 )alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO ₂ , C _1-6 haloalkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [00143] In another embodiment, R ^b and R ^f are independently selected from hydrogen, C _1-6 alkyl, O-C _1-6 alkyl, C _6-12 aryl, C _6-12 aryl(C _1-3 )alkyl, wherein said C _1-6 alkyl, C _6-12 aryl, C _{6- 12} aryl(C _1-3 )alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO ₂ , C _1-6 haloalkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C _{1- 6} alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [00144] In another embodiment, R ^b and R ^f are independently selected from hydrogen, phenyl, phenyl(C1-3)alkyl, wherein said phenyl and phenyl(C1-3)alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO2, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. [00145] In one embodiment, wherein each R ^c and R ^g are independently selected from hydrogen, halogen, CN, C1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl and C6-15 aryl, wherein said C1-6 alkyl, C6-15 aryl, 3-7 membered heterocycloalkyl 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, nitro, amino, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl and O-C1-6 alkyl. [00146] In another embodiment, each R ^c and R ^g are independently selected from hydrogen, C1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl and C6-12 aryl, wherein said C1-6 alkyl, C6-15 aryl, 3-7 membered heterocycloalkyl 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, nitro, amino, C1-6 haloalkyl, C3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl. [00147] In another embodiment, each R ^c and R ^g are independently selected from hydrogen, C _1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C _3-6 cycloalkyl, C _1-6 alkyl and phenyl, wherein said C _1-6 alkyl, C _6-15 aryl, 3-7 membered heterocycloalkyl 5-6 membered heteroaryl and C _3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, nitro, amino, C _1-6 haloalkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl. [00148] In another embodiment, each R ^c and R ^g are independently selected from hydrogen, C _1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C _1-6 alkyl and phenyl, wherein said C _1-6 alkyl, C _6-15 aryl, 3-7 membered heterocycloalkyl, and 5-6 membered heteroaryl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, nitro, amino, C _1-6 haloalkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl. [00149] In one embodiment, R ^d and R ^h are independently selected from hydrogen, CN, C _1-6 haloalkyl, C _3-6 cycloalkyl, and C _1-6 alkyl. [00150] In another embodiment, R ^d and R ^h are independently selected from hydrogen, C _3-6 cycloalkyl and C _1-6 alkyl. [00151] In another embodiment, R ^d and R ^h are independently selected from hydrogen, and C1-3 alkyl. [00152] In one embodiment, R ^e and R ^j are independently selected from hydrogen, CN, C1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-15 membered heteroaryl, C3-6 cycloalkyl, C1- 6 alkyl, O-C1-6 alkyl, C6-15 aryl, C6-15aryl(C1-6)alkyl, C3-11cycloalkyl(C1-6)alkyl, 4-15 membered heterocycloalkyl(C1-6)alkyl, and 4-15 membered heteroaryl(C1-6)alkyl, wherein said C1-6 alkyl, C6-15 aryl, 3-7 membered heterocycloalkyl, 5-15 membered heteroaryl, C3-6 cycloalkyl, C6- 15aryl(C1-6)alkyl, C3-11cycloalkyl(C1-6)alkyl, 4-15 membered heterocycloalkyl(C1-6)alkyl, and 4- 15 membered heteroaryl(C1-6)alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO2, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. [00153] In another embodiment, R ^e and R ^j are independently selected from hydrogen, CN, C1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-12 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, C6-12 aryl, C6-12aryl(C1-3)alkyl, C3-11cycloalkyl(C1-3)alkyl, 4-12 membered heterocycloalkyl(C _1-3 )alkyl, and 4-12 membered heteroaryl(C _1-3 )alkyl, wherein said C _1-6 alkyl, C _6-12 aryl, 3-7 membered heterocycloalkyl, 5-12 membered heteroaryl, C _3-6 cycloalkyl, C _{6- 12} aryl(C _1-3 )alkyl, C _3-11 cycloalkyl(C _1-3 )alkyl, 4-12 membered heterocycloalkyl(C _1-3 )alkyl, and 4- 12 membered heteroaryl(C _1-3 )alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO ₂ , C _1-6 haloalkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [00154] In another embodiment, R ^e and R ^j are independently selected from hydrogen, 3-7 membered heterocycloalkyl, 5-12 membered heteroaryl, C _3-6 cycloalkyl, C _1-6 alkyl, C _6-12 aryl, C _6-12 aryl(C _1-3 )alkyl, C _3-11 cycloalkyl(C _1-3 )alkyl, 4-12 membered heterocycloalkyl(C _1-3 )alkyl, and 4-12 membered heteroaryl(C _1-3 )alkyl, wherein said C _1-6 alkyl, C _6-12 aryl, 3-7 membered heterocycloalkyl, 5-12 membered heteroaryl, C _3-6 cycloalkyl, C _6-12 aryl(C _1-3 )alkyl, C _{3- 11} cycloalkyl(C _1-3 )alkyl, 4-12 membered heterocycloalkyl(C _1-3 )alkyl, and 4-12 membered heteroaryl(C _1-3 )alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO ₂ , C _1-6 haloalkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C _{1- 6} alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. [00155] In another embodiment, R ^e and R ^j are independently selected from hydrogen, C3-6 cycloalkyl, C1-6 alkyl, C6-12 aryl, C6-12aryl(C1-3)alkyl, C3-11cycloalkyl(C1-3)alkyl, wherein said C1-6 alkyl, C6-12 aryl, C3-6 cycloalkyl, C6-12aryl(C1-3)alkyl, and C3-11cycloalkyl(C1-3)alkyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO2, C1- 6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. [00156] In another embodiment, R ^e and R ^j are independently selected from hydrogen, C3-6 cycloalkyl, C1-6 alkyl, phenyl, pheny(C1-3)alkyl, C3-6cycloalkyl(C1-3)alkyl, wherein said C1-6 alkyl, phenyl, C3-6 cycloalkyl, phenyl(C1-3)alkyl, and C3-6cycloalkyl(C1-3)alkyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO2, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. [00157] In another embodiment, R ^e and R ^j are independently selected from hydrogen, C1-3 alkyl, phenyl, and pheny(C1-3)alkyl, wherein said C1-3 alkyl, phenyl and phenyl(C1-3)alkyl, , are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO2, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. [00158] In one embodiment, R ^d and R ^e , when attached to the same atom, together with the atom to which they are attached form a 5-7 membered ring, optionally containing one or more for heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more R ^k . [00159] In one embodiment, R ^h and R ^j , when attached to the same atom, together with the atom to which they are attached form a 5-7 membered ring, optionally containing one or more for heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more R ^k . [00160] In one embodiment, R ^k is selected from =O, halogen, CN, NH ₂ , NH(C _1-6 alkyl), N(C _1-6 alkyl) ₂ , C _1-6 haloalkyl, C _3-6 cycloalkyl, phenyl, 5-7 membered heterocycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl. [00161] In another embodiment, R ^k is selected from =O, halogen, CN, NH ₂ , NH(C _1-6 alkyl), N(C _1-6 alkyl) ₂ , C _1-6 haloalkyl, C _1-6 alkyl and O-C _1-6 alkyl. [00162] In another embodiment, R ^k is selected from =O, halogen, CN, NH ₂ , NH(C _1-3 alkyl), N(C ₁₃ alkyl) ₂ , C _1-6 haloalkyl, C _1-6 alkyl and O-C _1-6 alkyl. [00163] In another embodiment, R ^k is selected from =O, halogen, CN, NH ₂ , NHMe, N(Me) ₂ , C _1-3 haloalkyl, C _1-3 alkyl and O-C _1-3 alkyl. [00164] In one embodiment R’ and R’’ are independently selected from methyl, ethyl or propyl; preferably methyl or ethyl. [00165] In one embodiment, there is provided a compound of formula I, or a salt thereof, wherein: R is selected from the group consisting of C6-12aryl optionally substituted by one or more R ^a , 5-12 membered heterocycloalkyl optionally substituted by one or more R ^a , and 5-12 membered heteroaryl optionally substituted by one or more R ^a ; R ¹ is selected from the group consisting of hydrogen, C1-6alkyl optionally substituted by one or more R ^a1 , –C(=O)R ^b , and –C(=O)NR ^d R ^e ; R ² is selected from the group consisting of hydrogen, C1-6alkyl optionally substituted by one or more R ^a2 , C2-6alkenyl optionally substituted by one or more R ^a2 , phenyl optionally substituted by one or more R ^a2 , C3-7cycloalkyl optionally substituted by one or more R ^a2 , 4-7 membered heterocycloalkyl optionally substituted by one or more R ^a2 , and 5-6 membered heteroaryl optionally substituted by one or more R ^a2 ; or R ¹ and R ² together with the nitrogen atom to which they are attached form a 5-7 membered heterocycloalkyl ring or 5-6 membered heteroaryl ring, each independently and optionally containing one or more further heteroatoms selected from O, N, and S and wherein each ring is independently and optionally substituted with one or more R ^a3 ; R ³ is selected from the group consisting of H, C _1-6 alkyl, CN, –C(=O)R ^f , –C(=O)OR ^g , – C(=O)NR ^h R ^j , –S(=O) ₂ R ^g , –S(=O)R ^g , ––S(=O)NR ^h R ^j , and –S(=O) ₂ NR ^h R ^j , where said C _1-6 alkyl is optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _{1- 6} haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl; and R ⁴ is selected from the group consisting of hydrogen, C _1-6 alkyl optionally substituted by one or more R ^a4 , C _2-6 alkynyl optionally substituted by one or more R ^a4 , phenyl optionally substituted by one or more R ^a4, , benzyl optionally substituted by one or more R ^a4, , –C(=O)R ^f , –C(=O)OR ^g , –C(=O)NR ^h R ^j and –SR ^g . where R ^a , R ^a1 , R ^a2 , R ^a3 , R ^a4 , R ^b , R ^d , R ^e , R ^f , R ^g , R ^h , and R ^j are as defined in any one of the above mentioned embodiments. [00166] Suitably, R ³ is selected from the group consisting of H, C f 1-3 alkyl, CN, –C(=O)R and –C(=O)NR ^h R ^j , where said C1-3 alkyl is optionally substituted with one or more groups selected from hydroxyl, CN, C1-3 haloalkyl, C1-3 haloalkoxy, C3-6 cycloalkyl, and O-C1-3 alkyl [00167] In another embodiment, there is provided a compound of formula I, or a salt thereof, wherein: R is selected from the group consisting of phenyl optionally substituted by one or more R ^a , 5- 7 membered heterocycloalkyl optionally substituted by one or more R ^a , and 5-6 membered heteroaryl optionally substituted by one or more R ^a , wherein R ^a is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, where said C1-6 alkyl and O-C1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl; R ¹ is hydrogen or C1-6alkyl optionally substituted by one or more R ^a1 ; R ² is selected from the group consisting of hydrogen, C1-6alkyl optionally substituted by one or more R ^a2 , C2-6alkenyl optionally substituted by one or more R ^a2 , phenyl optionally substituted by one or more R ^a2 , C3-7cycloalkyl optionally substituted by one or more R ^a2 , 4-7 membered heterocycloalkyl optionally substituted by one or more R ^a2 , and 5-6 membered heteroaryl optionally substituted by one or more R ^a2 ; or R ¹ and R ² together with the nitrogen atom to which they are attached form a 3-12 membered heterocycloalkyl ring or 4-12 membered heteroaryl ring, each independently and optionally containing one or more further heteroatoms selected from O, N, and S and wherein each ring is independently and optionally substituted with one or more R ^a3 ; R ³ is selected from the group consisting of H, C _1-3 alkyl, CN, –C(=O)R ^f and –C(=O)NR ^h R ^j , where said C _1-3 alkyl is optionally substituted with one or more groups selected from hydroxyl, CN, C _1-3 haloalkyl, C _1-3 haloalkoxy, C _3-6 cycloalkyl, and O-C _1-3 alkyl; and R ⁴ is selected from the group consisting of hydrogen, C _1-6 alkyl optionally substituted by one or more R ^a4 , C _2-6 alkynyl optionally substituted by one or more R ^a4 , phenyl optionally substituted by one or more R ^a4, , benzyl optionally substituted by one or more R ^a4, , –C(=O)R ^f , –C(=O)OR ^g , –C(=O)NR ^h R ^j and –SR ^g . where R ^a , R ^a1 , R ^a2 , R ^a3 , R ^a4 , R ^f , R ^g , R ^h , and R ^j are as defined in any one of the above mentioned embodiments. Process for Preparation of Formula I [00168] In one aspect the present invention relates to a process for preparing a compound of formula I, or a salt thereof, wherein formula I is defined in any of the foregoing aspects and embodiments. [00169] A compound of formula I, in one embodiment, is prepared according to Scheme 1 (below): Scheme 1 [00170] In one aspect, the present invention relates to a process for preparing a compound of formula I, or a salt thereof: (I), comprising: (i) deprotecting a compound of formula II:

(II), to yield a compound of formula Ia: (Ia); and/or reacting a compound of formula Ia with a reactant suitable for introducing group R ³ to give a compound of formula Ib: (Ib); and/or deprotecting a compound of formula Ib to yield a compound of formula Ic:

(Ic); and/or and reacting a compound of formula Ic with a reactant suitable for introducing group R ⁴ to give a compound of formula I; and (ii) optionally preparing a salt of formula I; wherein: P ² is a nitrogen protecting group selected from tert-octyl, tert-butyl and Si(R ⁵ )3 wherein R ⁵ is selected from a C1-4 alkyl group or a phenyl group; P ³ is a nitrogen protecting of formula -SO ₂ R ⁶ wherein R ⁶ is selected from C _1-6 alkyl, C _{1- 6} haloalkyl, -CH ₂ CH ₂ SiMe ₃ , or a phenyl group optionally substituted with one or more groups selected from NO _2, halogen and methyl; and R, R ¹ , R ² , R ³ and R ⁴ are as defined in any one of the foregoing aspects and embodiments of the invention. [00171] In one embodiment, P ² is selected from tert-octyl, tert-butyl, triisopropylsilyl (TIPS), tert-butyldimethylsilyl (TBDMS), tert-butyldiphenylsilyl (TBDPS) and trimethylsilyl (TMS). [00172] In another embodiment, P ² is selected from tert-octyl, tert-butyl and TIPS. [00173] In another embodiment, P ² is selected from tert-octyl and tert-butyl, suitably tert-octyl. [00174] In one embodiment, P ³ is selected from nosyl, tosyl, brosyl, mesyl, 2- (Trimethylsilyl)ethanesulfonyl (SES), and tert-Butylsulfonyl (Bus). [00175] In another embodiment, P ³ is selected from nosyl, tosyl, brosyl and mesyl. [00176] In another embodiment, P ³ is selected from nosyl and tosyl, suitably nosyl. [00177] In one embodiment, P ² is t-octyl or TIPS and P ³ is nosyl. [00178] In one embodiment, P ² is selected from tert-octyl and tert-butyl, and the deprotection of the compound of formula II is carried out by treatment with acid. In one embodiment, the acid is a strong acid. In one embodiment, the acid is selected from trifluoroacetic acid (TFA), methanesulfonic acid (MsOH), trifluoromethanesulfonic acid (TfOH). Suitably, the acid is TFA. In one embodiment, an excess of TFA is used to deprotect formula II to give a compound of formula Ia, suitably in DCM at ambient temperature. [00179] In one embodiment, P ² is Si(R ⁵ )3 and a source of fluoride is used in the deprotection of the compound of formula II to give a compound of formula Ia. Suitably, the source of fluoride is selected from tetra-n-butylammonium fluoride (TBAF), cesium fluoride, potassium fluoride and HF. [00180] In one embodiment, the reactant suitable for introducing group R ³ is R ³ -X ² wherein X ² is a leaving group. Suitably, X ² is halo, for instance Cl or Br. [00181] In another embodiment, the reactant suitable for introducing group R ³ is R ^j - N=C=O, when R ³ is –C(=O)NR ^h R ^j , and R ^h is H. [00182] In another embodiment, the reactant suitable for introducing group R ³ is R ³ - CHO, when R ³ is C _1-6 alkyl. Suitably, this reaction is performed in the presence of a reducing agent, such a hydride reducing agent, for instance sodium borohydride (NaBH ₄ ), sodium triacetoxyborohydride (NaBH(OAc) ₃ ), or sodium cyanoborohydride (NaCNBH ₃ ). [00183] In one embodiment, P ³ is a nosyl group and the deprotection of formula Ib to give a compound according to formula Ic is performed using a thiolate nucleophile. Suitable thiolate nucleophiles are, for example, thiophenol, thioglycolic acid and C ₁ - ₂₀ alkyl-SH. Removal of the nosyl may be carried out in the presence of a base, such a carbonate or hydroxide base. Non-nucleophilic bases can also be used such as DBU. [00184] In one embodiment, P ³ is nosyl and the deprotection of formula Ib to give a compound according to formula Ic is performed using C ₁₂ alkyl-SH and DBU. Suitably, in acetonitrile at about 0°C. [00185] In another embodiment, P ³ is nosyl and the and the deprotection of formula Ib to give a compound according to formula Ic is performed using a reducing agent, such as sodium amalgam (Na(Hg)), aluminium amalgam, magnesium, samarium(II) iodide), tin hydrides (tributyltin hydride) and transition metal complexes with reducing agents. [00186] In another embodiment, P ³ is SES and the deprotection of formula Ib to give a compound according to formula Ic is performed using a source of fluoride. Suitably, the source of fluoride is selected from TBAF, cesium fluoride, potassium fluoride and HF. [00187] In another embodiment, P ³ is Bus, tosyl, brosyl and mesyl and the deprotection of formula Ib to give a compound according to formula Ic is performed using an acid. In one embodiment, the acid is a strong acid. In one embodiment, the acid is selected from TFA, MsOH, TfOH. Suitably, the acid is TFA. In one embodiment, an excess of TFA is used to deprotect formula Ib to give a compound of formula Ic, suitably in dichloromethane (DCM) at ambient temperature. [00188] In one embodiment, the reactant suitable for introducing group R ⁴ is selected from: (i) R ⁴ -B ¹ when R ⁴ is C _6-15 aryl optionally substituted by one or more R ^a4 or 4-15 membered heteroaryl optionally substituted by one or more R ^a4 , C _2-10 alkenyl optionally substituted by one or more R ^a4 and C _2-6 alkynyl optionally substituted by one or more R ^a4 , and wherein B ¹ is a boronic acid, a boronic acid ester, a cyclic boronic acid ester, an organotrifluoroborate potassium salt, cyclic triolborate, organoborane, or MIDA boronate; (ii) X ³ -C(=O)OR ^g when R ⁴ is –C(=O)OR ^g , wherein X ³ is a leaving group, suitably halo, for instance Cl, Br or I; (iii) R ⁴ -X ⁴ when R ⁴ is C _1-10 alkyl optionally substituted by one or more R ^a4 , C _2-10 alkenyl optionally substituted by one or more R ^a4 , C _2-6 alkynyl optionally substituted by one or more R ^a4 , C _6-15 aryl optionally substituted by one or more R ^a4 , 4-15 membered heteroaryl optionally substituted by one or more R ^a4 , C _6-15 aryl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , C(=O)NR ^h R ^j , –C(=O)R ^f , –S(=O) ₂ R ^g , –S(=O)R ^g , –S(=O)NR ^h R ^j and –S(=O) ₂ NR ^h R ^j and wherein X ⁴ is a leaving group, suitably halo, for instance F, Cl, Br or I; (iv) TMS-R ⁴ when R ⁴ is CF ₃ or CN. [00189] In one embodiment, the process for preparation of formula I further comprises preparing a compound of formula II (II), comprising reacting a compound of formula III: (III), with a compound of formula IV: H-NR1R2 (IV); wherein X is a leaving group; and R, R ¹ , R ² , P ² and P ³ are as defined in any of the foregoing aspects and embodiments. [00190] In one embodiment, X is halo, suitably F. [00191] In another embodiment, X is a nitrogen azole, in particular imidazole or triazole. [00192] In one embodiment, the reaction between formula III and formula IV is conducted in the presence of a Lewis acid. Suitably, the Lewis acid is a triflimide salt. In particular a triflimide salt selected from Ca(NTf)2 or Ba(NTf)2. [00193] In one embodiment, the reaction between formula III and formula IV is conducted in the presence of a Lewis acid, suitably as defined above, in a protic solvent, such as an alcohol or water. In one embodiment, the alcohol is a C3-C6 alcohol, suitably t-amyl alcohol or t-butanol. [00194] In another embodiment, the reaction between formula III and formula IV is additionally conducted in the presence of a base. Suitable bases are amines, for instance, 1,4-diazabicyclo[2.2.2]octane (DABCO) and other trialkylamines, such as triethylamine or N,N- diisopropylethylamine (DIPEA). In one embodiment, the reaction is between formula III and formula IV is additionally conducted in the presence of a Lewis acid and a base, suitably Ca(NTf)2 and DABCO. [00195] In another embodiment, the reaction between formula III and formula IV is conducted with a fluoride scavenger and a catalyst. Suitably, the fluoride scavenger is a silicon compound, such as a silane or siloxane. Suitable silicon compounds are, for instance, 1,1,3,3-tetramethyldisiloxane (TMDS), polymethylhydrosiloxane (PMHS), and (EtO)2MeSiH. [00196] In one embodiment, the catalyst is hydroxybenzotriazole (HOBt). In one embodiment, the reaction between formula III and formula IV is conducted with HOBt and TMDS. [00197] In one embodiment, the process for preparation of formula I further comprises preparing a compound of formula III: (III), comprising reaction a compound of formula V: with a halogenating agent; wherein R, X, P ² and P ³ are as defined in any of the foregoing embodiments and aspects of the invention. [00198] In one embodiment, X is F and the halogenating agent is a fluorinating agent. Suitably, the fluorinating agent is selected from N-fluorobenzenesulfonimide (NFSI), N-fluoro- o-benzenedisulfonimide (NFOBS) and Selectfluor. In one embodiment, the fluorinating agent is NFSI. Suitably the fluorination is carried out at about 0°C. [00199] In one embodiment, the compound of formula V is first treated with a base and subsequently treated with the halogenating agent. In one embodiment, the base is a hydride reagent, such as sodium hydride. In one embodiment, the base is sodium hydride and the halogenating agent is a fluorinating agent, for instance NFSI. [00200] In one embodiment, the process for preparation of formula I further comprises preparing a compound of formula V: (V), comprising protecting a compound of formula VI: (VI), with a nitrogen protecting group P ³ ; wherein R, P ² and P ³ are as defined any of the above-mentioned aspects and embodiments. [00201] In one embodiment, P ³ is -SO ₂ R ⁶ and the compound VI is protected by reacting with a R ⁶ SO ₂ X ⁵ , wherein X ⁵ is a leaving group, suitably halo, for instance Cl, Br or I. Suitably, the reaction is conducted in the presence of a base, for instance trialkylamines, such as triethylamine or DIPEA. [00202] In one embodiment, P ³ is nosyl and the compound of formula VI is protected by reaction with NsCl. [00203] In one embodiment, the process for preparation of formula I further comprises preparing a compound of formula VI: (VI), comprising reacting a compound of formula VII: with an organometallic reactant compound of formula VIII: R-M (VIII) wherein P ¹ is a nitrogen protecting group selected from a group of formula Si(R ⁷ ) 7 3 wherein R is independently selected from C1-4 alkyl and a phenyl group; M is a metallic moiety; and R and P ² are as defined in any one of the foregoing aspects or embodiments. [00204] In one embodiment, the metallic moiety of formula VIII is lithium. In another embodiment, the metallic moiety of formula VIII is MgX ⁶ , wherein X ⁶ is halo, suitably Cl, Br or I, more suitably Cl or Br. [00205] In one embodiment, R ⁷ is a C1-4 alkyl group. In another embodiment, R ⁷ is selected from methyl, ethyl or isopropyl. Suitably, each R ⁷ is methyl (i.e. P ¹ is TMS). [00206] In one embodiment, P ¹ and P ² are not the same protecting group. In one embodiment, when P ² is a silicon protecting group, the silicon atom of P ¹ is less sterically hindered than the silicon atom of P ² . [00207] In one embodiment, P ¹ is TMS or TIPS, suitably TMS. [00208] In one embodiment, P ¹ is TMS and P ² is TIPS. [00209] In one embodiment, P ¹ is TMS or TIPS and P ² is t-octyl. [00210] In another embodiment, P ¹ is TMS and P ² is t-octyl. [00211] In another embodiment, P ¹ is TMS or TIPS and P ² is TBDPS or TBDMS. [00212] In another embodiment, P ¹ is TIPS and P ² is TBDPS. [00213] Suitably, the reaction between formula VII and formula VIII is conducted in an ether solvent, for instance THF or diethyl ether. [00214] In one embodiment, the process for preparation of formula I further comprises preparing a compound of formula VII: from a compound of formula IX: [00215] In one embodiment, formula VII is prepared from formula IX by reacting formula IX with P ¹ -X ⁷ and a base, wherein X ⁷ is halo, suitably Cl or Br. [00216] In one embodiment, when P ¹ is TMS, formula VII is prepared from formula IX by reacting formula IX with LiHMDS and TMSCl. [00217] In one embodiment, the compounds of formula VI and/or the compound of VII is not isolated prior to the following step. Intermediates and processes for their preparation [00218] In one aspect of the invention there is provided a compound of formula II, or a salt thereof: (II) wherein R, R ¹ , R ² , P ² and P ³ are as defined in any of the afore-mentioned aspects or embodiments. [00219] In one embodiment, P ³ is a nosyl group. [00220] In another embodiment, P ² is a t-octyl group or TIPS. [00221] In one embodiment, P ³ is a nosyl group and P ² is a t-octyl or TIPS group. [00222] In another aspect of the invention, there is provided a process for the preparation of a compound of formula II, or a salt thereof, comprising reacting a compound of formula III: (III), with a compound of formula IV: H-NR1R2 (IV), wherein R, R ¹ , R ² , P ² , P ³ and X are as defined in any of the afore-mentioned aspects or embodiments. [00223] In one embodiment, X is halo, suitably F. [00224] In another embodiment, X is selected from a nitrogen azole, in particular imidazole or triazole. [00225] In one embodiment, the reaction between formula III and formula IV is conducted in the presence of a Lewis acid. Suitably, the Lewis acid is a triflimide salt. In particular a triflimide salt selected from Ca(NTf)2 or Ba(NTf)2. [00226] In one embodiment, the reaction between formula III and formula IV is conducted in the presence of a Lewis acid, suitably as defined above, in a protic solvent, such as an alcohol or water. In one embodiment, the alcohol is a C3-C6 alcohol, suitably t-amyl alcohol or t-butanol. [00227] In another embodiment, the reaction between formula III and formula IV is additionally conducted in the presence of a base. Suitable bases are amines, for instance, DABCO or DIPEA. In one embodiment, the reaction is between formula III and formula IV is additionally conducted in the presence of a Lewis acid and a base, suitably Ca(NTf)2 and DABCO. [00228] In another embodiment, the reaction between formula III and formula IV is conducted with a fluoride scavenger and a catalyst. Suitably, the fluoride scavenger is a silicon compound, such as a silane or siloxane. Suitable silicon compounds are, for instance, 1,1,3,3-tetramethyldisiloxane (TMDS), polymethylhydrosiloxane (PMHS), and (EtO)2MeSiH. [00229] In one embodiment, the catalyst is hydroxybenzotriazole (HOBt). In one embodiment, the reaction between formula III and formula IV is conducted with HOBt and TMDS. [00230] In one embodiment, the process for preparation of formula II further comprises preparing a compound of formula III: (III), comprising reaction a compound of formula V: with a halogenating agent; wherein R, P ² and P ³ are as defined in any of the foregoing embodiments and aspects of the invention. [00231] In one embodiment, X is F and the halogenating agent is a fluorinating agent. Suitably, the fluorinating agent is selected from N-fluorobenzenesulfonimide (NFSI), N-fluoro- o-benzenedisulfonimide (NFOBS) and Selectfluor. In one embodiment, the fluorinating agent is NFSI. Suitably the fluorination is carried out at about 0°C. [00232] In one embodiment, the compound of formula V is first treated with a base and subsequently treated with the halogenating agent. In one embodiment, the base is a hydride reagent, such as sodium hydride. In one embodiment, the base is sodium hydride and the halogenating agent is a fluorinating agent, for instance NFSI. [00233] In one embodiment, the process for preparation of formula II further comprises preparing a compound of formula V: (V), comprising protecting a compound of formula VI: (VI), with a nitrogen protecting group P ³ ; wherein R, P ² and P ³ are as defined any of the above-mentioned aspects and embodiments. [00234] In one embodiment, P ³ is -SO ₂ R ⁶ and the compound VI is protected by reacting with a R ⁶ SO ₂ X ⁵ , wherein X ⁵ is a leaving group, suitably halo, for instance Cl, Br or I. Suitably, the reaction is conducted in the presence of a base, for instance triethylamine or DIPEA. [00235] In one embodiment, P ³ is nosyl and the compound of formula VI is protected by reaction with NsCl. [00236] In one embodiment, the process for preparation of formula II further comprises preparing a compound of formula VI: (VI), comprising reacting a compound of formula VII: with an organometallic reactant compound of formula VIII: R-M (VIII) wherein P ¹ is a nitrogen protecting group selected from a group of formula Si(R ⁷ ) 7 3 wherein R is independently selected from C1-4 alkyl and a phenyl group; M is a metallic moiety; and R and P ² are as defined in any one of the foregoing aspects or embodiments. [00237] In one embodiment, the metallic moiety of formula VIII is lithium. In another embodiment, the metallic moiety of formula VIII is MgX ⁶ , wherein X ⁶ is halo, suitably Cl, Br or I, more suitably Cl or Br. [00238] In one embodiment, R ⁷ is a C1-4 alkyl group. In another embodiment, R ⁷ is selected from methyl, ethyl or isopropyl. Suitably, each R ⁷ is methyl (i.e. P ¹ is TMS). [00239] In one embodiment, P ¹ and P ² are not the same protecting group. In one embodiment, when P ² is a silicon protecting group, the silicon atom of P ¹ is less sterically hindered than the silicon atom of P ² . [00240] In one embodiment, P ¹ is TMS or TIPS, suitably TMS. [00241] In one embodiment, P ¹ is TMS and P ² is TIPS. [00242] In one embodiment, P ¹ is TMS or TIPS and P ² is t-octyl. [00243] In another embodiment, P ¹ is TMS and P ² is t-octyl. [00244] In another embodiment, P ¹ is TMS or TIPS and P ² is TBDPS or TBDMS. [00245] In another embodiment, P ¹ is TIPS and P ² is TBDPS. [00246] Suitably, the reaction between formula VII and formula VIII is conducted in an ether solvent, for instance THF or diethyl ether. [00247] In one embodiment, the process for preparation of formula II further comprises preparing a compound of formula VII: from a compound of formula IX: [00248] In one embodiment, formula VII is prepared from formula IX by reacting formula IX with P ¹ -X ⁷ and a base, wherein X ⁷ is halo, suitably Cl or Br. [00249] In one embodiment, when P ¹ is TMS, formula VII is prepared from formula IX by reacting formula IX with LiHMDS and TMSCl. [00250] In one embodiment, the compounds of formula VI and/or the compound of VII is not isolated prior to the following step. [00251] In another aspect of the invention, there is provided a compound of formula III or a salt thereof: (III), wherein R, P ² and P ³ are as defined in any of the afore-mentioned embodiments. [00252] In one embodiment, P ³ is a nosyl group. [00253] In another embodiment, P ² is a t-octyl or TIPS group. [00254] In one embodiment, P ³ is a nosyl group and P ² is a t-octyl or TIPS group. [00255] In one embodiment, X is F. Suitably X is F, P ³ is a nosyl group and P ² is a t- octyl or TIPS group. [00256] In another aspect of the invention, there is provided a process for the preparation of a compound of formula III, or a salt thereof: (III), comprising reaction a compound of formula V: with a halogenating agent, wherein R, P ² , P ³ and X are defined in any of the fore-going aspects or embodiments. [00257] In one embodiment, X is F and the halogenating agent is a fluorinating agent. Suitably, the fluorinating agent is selected from N-fluorobenzenesulfonimide (NFSI), N-fluoro- o-benzenedisulfonimide (NFOBS) and Selectfluor. In one embodiment, the fluorinating agent is NFSI. Suitably the fluorination is carried out at about 0°C. [00258] In one embodiment, the compound of formula V is first treated with a base and subsequently treated with the halogenating agent. In one embodiment, the base is a hydride reagent, such as sodium hydride. In one embodiment, the base is sodium hydride and the halogenating agent is a fluorinating agent, for instance NFSI. [00259] In one embodiment, the process for preparation of formula III further comprises preparing a compound of formula V: (V), comprising protecting a compound of formula VI: (VI), with a nitrogen protecting group P ³ ; wherein R, P ² and P ³ are as defined any of the above-mentioned aspects and embodiments. [00260] In one embodiment, P ³ is -SO ₂ R ⁶ and the compound VI is protected by reacting with a R ⁶ SO ₂ X ⁵ , wherein X ⁵ is a leaving group, suitably halo, for instance Cl, Br or I. Suitably, the reaction is conducted in the presence of a base, for instance triethylamine or DIPEA. [00261] In one embodiment, P ³ is nosyl and the compound of formula VI is protected by reaction with NsCl. [00262] In one embodiment, the process for preparation of formula III further comprises preparing a compound of formula VI: (VI), comprising reacting a compound of formula VII: (VII) with an organometallic reactant compound of formula VIII: R-M (VIII) wherein P ¹ is a nitrogen protecting group selected from a group of formula Si(R ⁷ ) ₃ wherein R7 is independently selected from C _1-4 alkyl and a phenyl group; M is a metallic moiety; and R and P ² are as defined in any one of the foregoing aspects or embodiments. [00263] In one embodiment, the metallic moiety of formula VIII is lithium. In another embodiment, the metallic moiety of formula VIII is MgX ⁶ , wherein X ⁶ is halo, suitably Cl, Br or I, more suitably Cl or Br. [00264] In one embodiment, R ⁷ is a C _1-4 alkyl group. In another embodiment, R ⁷ is selected from methyl, ethyl or isopropyl. Suitably, each R ⁷ is methyl (i.e. P ¹ is TMS). [00265] In one embodiment, P ¹ and P ² are not the same protecting group. In one embodiment, when P ² is a silicon protecting group, the silicon atom of P ¹ is less sterically hindered than the silicon atom of P ² . [00266] In one embodiment, P ¹ is TMS or TIPS, suitably TMS. [00267] In one embodiment, P ¹ is TMS and P ² is TIPS. [00268] In one embodiment, P ¹ is TMS or TIPS and P ² is t-octyl. [00269] In another embodiment, P ¹ is TMS and P ² is t-octyl. [00270] In another embodiment, P ¹ is TMS or TIPS and P ² is TBDPS or TBDMS. [00271] In another embodiment, P ¹ is TIPS and P ² is TBDPS. [00272] Suitably, the reaction between formula VII and formula VIII is conducted in an ether solvent, for instance THF or diethyl ether. [00273] In one embodiment, the process for preparation of formula III further comprises preparing a compound of formula VII: (VII) from a compound of formula IX: [00274] In one embodiment, formula VII is prepared from formula IX by reacting formula IX with P ¹ -X ⁷ and a base, wherein X ⁷ is halo, suitably Cl or Br. [00275] In one embodiment, when P ¹ is TMS, formula VII is prepared from formula IX by reacting formula IX with LiHMDS and TMSCl. [00276] In one embodiment, the compounds of formula VI and/or the compound of VII is/are not isolated prior to the following step. [00277] In another aspect, the present invention relates to a compound of formula V, or a salt thereof: wherein R, P ² and P ³ are as defined in any of the foregoing aspects or embodiments. [00278] In one embodiment, P ³ is a nosyl group. [00279] In another embodiment, P ² is a t-octyl or TIPS group. [00280] In one embodiment, P ³ is a nosyl group and P ² is a t-octyl or TIPS group. [00281] In another aspect of the invention, there is provided a process for the preparation of a compound of formula V, or a salt thereof, comprising protecting a compound of formula VI: (VI), with a nitrogen protecting group P ³ ; wherein R, P ² and P ³ are as defined any of the above-mentioned aspects and embodiments. [00282] In one embodiment, P ³ is -SO ₂ R ⁶ and the compound VI is protected by reacting with a R ⁶ SO ₂ X ⁵ , wherein X ⁵ is a leaving group, suitably halo, for instance Cl, Br or I. Suitably, the reaction is conducted in the presence of a base, for instance triethylamine or DIPEA. [00283] In one embodiment, P ³ is nosyl and the compound of formula VI is protected by reaction with NsCl. [00284] In one embodiment, the process for preparation of formula V further comprises preparing a compound of formula VI: (VI), comprising reacting a compound of formula VII: with an organometallic reactant compound of formula VIII: R-M (VIII) wherein P ¹ is a nitrogen protecting group selected from a group of formula Si(R ⁷ ) ₃ wherein R7 is independently selected from C _1-4 alkyl and a phenyl group; M is a metallic moiety; and R and P ² are as defined in any one of the foregoing aspects or embodiments. [00285] In one embodiment, the metallic moiety of formula VIII is lithium. In another embodiment, the metallic moiety of formula VIII is MgX ⁶ , wherein X ⁶ is halo, suitably Cl, Br or I, more suitably Cl or Br. [00286] In one embodiment, R ⁷ is a C1-4 alkyl group. In another embodiment, R ⁷ is selected from methyl, ethyl or isopropyl. Suitably, each R ⁷ is methyl (i.e. P ¹ is TMS). [00287] In one embodiment, P ¹ and P ² are not the same protecting group. In one embodiment, when P ² is a silicon protecting group, the silicon atom of P ¹ is less sterically hindered than the silicon atom of P ² . [00288] In one embodiment, P ¹ is TMS or TIPS, suitably TMS. [00289] In one embodiment, P ¹ is TMS and P ² is TIPS. [00290] In one embodiment, P ¹ is TMS or TIPS and P ² is t-octyl. [00291] In another embodiment, P ¹ is TMS and P ² is t-octyl. [00292] In another embodiment, P ¹ is TMS or TIPS and P ² is TBDPS or TBDMS. [00293] In another embodiment, P ¹ is TIPS and P ² is TBDPS. [00294] Suitably, the reaction between formula VII and formula VIII is conducted in an ether solvent, for instance THF or diethyl ether. [00295] In one embodiment, the process for preparation of formula V further comprises preparing a compound of formula VII: from a compound of formula IX: [00296] In one embodiment, formula VII is prepared from formula IX by reacting formula IX with P ¹ -X ⁷ and a base, wherein X ⁷ is halo, suitably Cl or Br. [00297] In one embodiment, when P ¹ is TMS, formula VII is prepared from formula IX by reacting formula IX with LiHMDS and TMSCl. [00298] In one embodiment, the compounds of formula VI and/or the compound of VII is not isolated prior to the following step. [00299] In one aspect of the invention, there is provided a compound of formula VI, or a salt thereof: (VI), wherein R and P ² are as defined in any of the afore-mentioned aspects or embodiments. [00300] In another embodiment, P ² is a t-octyl or TIPS group. [00301] In another aspect, the present invention provides a process for the preparation of a compound of formula VI: (VI), comprising reacting a compound of formula VII: with a compound of formula VIII: R-M (VIII); wherein R, M, P ¹ and P ² are as defined in any of the afore mentioned aspects or embodiments. [00302] In one embodiment, the metallic moiety of formula VIII is lithium. In another embodiment, the metallic moiety of formula VIII is MgX ⁶ , wherein X ⁶ is halo, suitably Cl, Br or I, more suitably Cl or Br. [00303] In one embodiment, R ⁷ is a C1-4 alkyl group. In another embodiment, R ⁷ is selected from methyl, ethyl or isopropyl. Suitably, each R ⁷ is methyl (i.e. P ¹ is TMS). [00304] In one embodiment, R ⁷ is selected from methyl, ethyl or isopropyl. [00305] In one embodiment, P ¹ is TMS or TIPS, suitably TMS. In one embodiment, P ² is t-octyl or TIPS. [00306] In one embodiment, P ¹ and P ² are not the same protecting group. In one embodiment, when P ² is a silicon protecting group, the silicon atom of P ¹ is less sterically hindered than the silicon atom of P ² . [00307] In one embodiment, P ¹ is TMS and P ² is TIPS. [00308] In one embodiment, P ¹ is TMS or TIPS and P ² is t-octyl. [00309] In another embodiment, P ¹ is TMS and P ² is t-octyl. [00310] In another embodiment, P ¹ is TMS or TIPS and P ² is TBDPS or TBDMS. [00311] In another embodiment, P ¹ is TIPS and P ² is TBDPS. [00312] Suitably, the reaction between formula VII and formula VIII is conducted in an ether solvent, for instance THF or diethyl ether. [00313] In one embodiment, the process for preparation of formula VI further comprises preparing a compound of formula VII: from a compound of formula IX: [00314] In one embodiment, formula VII is prepared from formula IX by reacting formula IX with P ¹ -X ⁷ and a base, wherein X ⁷ is halo, suitably Cl or Br. [00315] In one embodiment, when P ¹ is TMS, formula VII is prepared from formula IX by reacting formula IX with LiHMDS and TMSCl. [00316] In one embodiment, the compounds of formula VI and/or the compound of VII is not isolated prior to the following step. [00317] In another aspect, the present invention provides a compound of formula Ic, or a salt thereof: (Ic), wherein R, R ¹ , R ² and R ³ are as defined in any of the afore-mentioned aspects or embodiments. [00318] In another aspect, the present invention provides a compound of formula Ib, or a salt thereof: (Ib), wherein R, R ¹ , R ² , R ³ and P ³ are as defined in any of the afore-mentioned aspects or embodiments. [00319] Suitably, P ³ is a nosyl group. [00320] In another aspect, the present invention provides a compound of formula Ia, or a salt thereof:

(Ia), wherein R, R ¹ , R ² , and P ³ are as defined in any of the afore-mentioned aspects or embodiments. [00321] Suitably, P ³ is a nosyl group. Salts [00322] The compounds (including final products and intermediates) described herein may be isolated and used per se or may be isolated in the form of a salt, suitably pharmaceutically acceptable salts. It should be understood that the terms “salt(s)” and “salt form(s)” used by themselves or in conjunction with another term or terms encompasses all inorganic and organic salts, including industrially acceptable salts, as defined herein, and pharmaceutically acceptable salts, as defined herein, unless otherwise specified. As used herein, industrially acceptable salts are salts that are generally suitable for manufacturing and/or processing (including purification) as well as for shipping and storage, but may not be salts that are typically administered for clinical or therapeutic use. Industrially acceptable salts may be prepared on a laboratory scale, i.e. multi-gram or smaller, or on a larger scale, i.e. up to and including a kilogram or more. [00323] Pharmaceutically acceptable salts, as used herein, are salts that are generally chemically and/or physically compatible with the other ingredients comprising a formulation, and/or are generally physiologically compatible with the recipient thereof. Pharmaceutically acceptable salts may be prepared on a laboratory scale, i.e. multi-gram or smaller, or on a larger scale, i.e. up to and including a kilogram or more. It should be understood that pharmaceutically acceptable salts are not limited to salts that are typically administered or approved by the FDA or equivalent foreign regulatory body for clinical or therapeutic use in humans. A practitioner of ordinary skill will readily appreciate that some salts are both industrially acceptable as well as pharmaceutically acceptable salts. It should be understood that all such salts, including mixed salt forms, are within the scope of the application. [00324] In one embodiment, the compounds of Formula I, Ia, Ib or Ic are isolated as pharmaceutically acceptable salts. [00325] A suitable pharmaceutically acceptable salt of a compound of the invention is, for example, an acid-addition salt of a compound of the invention which is sufficiently basic, for example, an acid-addition salt with, for example, an inorganic or organic acid, for example hydrochloric, hydrobromic, sulfuric, phosphoric, trifluoroacetic, formic, citric or maleic acid. In addition a suitable pharmaceutically acceptable salt of a compound of the invention which is sufficiently acidic is an alkali metal salt, for example a sodium or potassium salt, an alkaline earth metal salt, for example a calcium or magnesium salt, an ammonium salt or a salt with an organic base which affords a physiologically-acceptable cation, for example a salt with methylamine, dimethylamine, trimethylamine, piperidine, morpholine or tris-(2-hydroxyethyl)amine. [00326] In general, salts of the present application can be prepared in situ during the isolation and/or purification of a compound (including intermediates), or by separately reacting the compound (or intermediate) with a suitable organic or inorganic acid or base (as appropriate) and isolating the salt thus formed. The degree of ionisation in the salt may vary from completely ionised to almost non-ionised. In practice, the various salts may be precipitated (with or without the addition of one or more co-solvents and/or anti-solvents) and collected by filtration or the salts may be recovered by evaporation of solvent(s). Salts of the present application may also be formed via a “salt switch” or ion exchange/double displacement reaction, i.e. reaction in which one ion is replaced (wholly or in part) with another ion having the same charge. One skilled in the art will appreciate that the salts may be prepared and/or isolated using a single method or a combination of methods. [00327] Representative salts include, but are not limited to, acetate, aspartate, benzoate, besylate, bicarbonate/carbonate, bisulphate/sulphate, borate, camsylate, citrate, edisylate, esylate, formate, fumarate, gluceptate, gluconate, glucuronate, hexafluorophosphate, hibenzate, hydrochloride/chloride, hydrobromide/bromide, hydroiodide/iodide, isethionate, lactate, malate, maleate, malonate, mesylate, methylsulphate, naphthylate, 2-napsylate, nicotinate, nitrate, orotate, oxalate, palmitate, pamoate, phosphate/hydrogen phosphate/dihydrogen phosphate, saccharate, stearate, succinate, tartrate, tosylate, trifluoroacetate and the like. Other examples of representative salts include alkali or alkaline earth metal cations such as sodium, lithium, potassium, calcium, magnesium, and the like, as well as non-toxic ammonium, quaternary ammonium and amine cations including, but not limited to, ammonium, tetramethylammonium, tetraethylammonium, lysine, arginine, benzathine, choline, tromethamine, diolamine, glycine, meglumine, olamine and the like. Tautomers [00328] Compounds of the Formula I and the various intermediates useful in the preparation thereof may exist in a number of different tautomeric forms and references to compounds of the Formula I and the various intermediates useful in the preparation thereof include all such forms. For the avoidance of doubt, where a compound can exist in one of several tautomeric forms, and only one is specifically described or shown, all others are nevertheless embraced by the general formulae. Examples of tautomeric forms include keto-, enol-, and enolate- forms, as in, for example, the following tautomeric pairs: keto/enol (illustrated below), pyrimidone/hydroxypyrimidine, imine/enamine, amide/imino alcohol, amidine/amidine, nitroso/oxime, thioketone/enethiol, and nitro/aci-nitro. keto enol enolate [00329] For example, in respect of sulfinamidine compounds of the present invention depiction of one tautomeric form should be considered to embrace the other tautomeric forms unless specifically stated to the contrary: Isomers [00330] Compounds that have the same molecular formula but differ in the nature or sequence of bonding of their atoms or the arrangement of their atoms in space are termed “isomers”. Isomers that differ in the arrangement of their atoms in space are termed “stereoisomers”. Stereoisomers that are not mirror images of one another are termed “diastereomers” and those that are non-superimposable mirror images of each other are termed “enantiomers”. When a compound has an asymmetric centre, for example, it is bonded to four different groups, a pair of enantiomers is possible. An enantiomer can be characterized by the absolute configuration of its asymmetric centre and is described by the R- and S-sequencing rules of Cahn and Prelog, or by the manner in which the molecule rotates the plane of polarized light and designated as dextrorotatory or levorotatory (i.e., as (+) or (-)-isomers respectively). A chiral compound can exist as either individual enantiomer or as a mixture thereof. A mixture containing equal proportions of the enantiomers is called a “racemic mixture”. [00331] Certain compounds of Formula I and the various intermediates useful in the preparation thereof, particularly Formulae Ia, Ib, Ic, III and III, may have one or more asymmetric centres and therefore can exist in a number of stereoisomeric configurations. Consequently, such compounds can be synthesized and/or isolated as mixtures of enantiomers and/or as individual (pure) enantiomers, and, in the case of two or more asymmetric centers, single diastereomers and/or mixtures of diastereomers. It should be understood that the present application includes all such enantiomers and diastereomers and mixtures thereof in all ratios, unless expressly stated otherwise. [00332] A person skilled in the art will appreciate that certain compounds, or salts thereof of the present invention, may contain at least one chiral centre, for instance at sulphur. The compounds or salts thereof, may therefore exist in at least two enantiomeric forms. The present invention encompasses racemic mixtures of the compounds, or salts thereof of the present invention as well as enantiomerically enriched and substantially enantiomerically pure isomers. As used herein, a “substantially enantiomerically pure” isomer of a compound comprises less than 5% of other enantiomers of the same compound, more typically less than 2%, and most typically less than 0.5% by weight. Isotopes [00333] The compounds of the present invention are described herein using structural formulas that do not specifically recite the mass numbers or the isotope ratios of the constituent atoms. As such it is intended that the present application includes compounds in which the constituent atoms are present in any ratio of isotope forms. For example, carbon atoms may be present in any ratio of ¹² C, ¹³ C, and ¹⁴ C; hydrogen atoms may be present in any ratio of ¹ H, ² H, and ³ H; etc. Preferably, the constituent atoms in the compounds of the present invention are present in their naturally occurring ratios of isotope forms. Numbered Paragraphs [00334] The invention will now be further described by way of the following numbered paragraphs: 1. A process for preparing a compound of formula I, or a salt thereof:

(I), comprising: (i) deprotecting a compound of formula II: (II), to yield a compound of formula Ia: (Ia); and/or reacting a compound of formula Ia with a reactant suitable for introducing group R ³ to give a compound of formula Ib:

(Ib), and/or deprotecting a compound of formula Ib to yield a compound of formula Ic: (Ic); and/or and reacting a compound of formula Ic with a reactant suitable for introducing group R ⁴ to give a compound of formula I; and (ii) optionally preparing a salt of formula I; wherein: P ² is a nitrogen protecting group selected from tert-octyl, tert-butyl and Si(R ⁵ ) ₃ wherein R ⁵ is selected from a C _1-4 alkyl group or a phenyl group; P ³ is a nitrogen protecting of formula -SO ₂ R ⁶ wherein R ⁶ is selected from C _1-6 alkyl, C _{1- 6} haloalkyl, CH ₂ CH ₂ SiMe ₃ , or a phenyl group optionally substituted with one or more groups selected from NO _2, halogen and methyl; and R ¹ is selected from the group consisting of hydrogen, C _1-10 alkyl optionally substituted by one or more R ^a1 , C _2-10 alkenyl optionally substituted by one or more R ^a1 , C _2-6 alkynyl optionally substituted by one or more R ^a1 , C _6-15 aryl optionally substituted by one or more R ^a1 , C _6-15 aryl(C _1-6 )alkyl optionally substituted by one or more R ^a1 , C _3-11 cycloalkyl optionally substituted by one or more R ^a1 , C3-11cycloalkyl(C1-6)alkyl optionally substituted by one or more R ^a1 , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a1 , 4-15 membered heterocycloalkyl(C1-6)alkyl optionally substituted by one or more R ^a1 , 4-15 membered heteroaryl optionally substituted by one or more R ^a1 , and 4-15 membered heteroaryl(C1-6)alkyl optionally substituted by one or more R ^a1 , –C(=O)R ^b , –C(=O)OR ^c , – C(=O)NR ^d R ^e , and –C(O)C(=O)R ^b ; where each R ^a1 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1- 6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , – NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O)2R ^b , –NR ^d S(=O)2NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , – OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O) ₂ R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O) ₂ R ^c , – OS(=O) ₂ OR ^c , –S(=O)NR ^d R ^e , –OS(=O) ₂ NR ^d R ^e , and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O- C _1-6 alkyl, C _3-6 cycloalkyl, and 3-7 membered heterocycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl; R ² is selected from the group consisting of hydrogen, C _1-10 alkyl optionally substituted by one or more R ^a2 , C _2-10 alkenyl optionally substituted by one or more R ^a2 , C _2-6 alkynyl optionally substituted by one or more R ^a2 , C _6-15 aryl optionally substituted by one or more R ^a2 , C _6-15 aryl(C _1-6 )alkyl optionally substituted by one or more R ^a2 , C _3-11 cycloalkyl optionally substituted by one or more R ^a2 , C _3-11 cycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a2 , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a2 , 4-15 membered heterocycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a2 , 4-15 membered heteroaryl optionally substituted by one or more R ^a2 , and 4-15 membered heteroaryl(C _1-6 )alkyl optionally substituted by one or more R ^a2 , –C(=O)R ^b , –C(=O)OR ^c , – C(=O)NR ^d R ^e , and –C(O)C(=O)R ^b ; where each R ^a2 is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _{1- 6} haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , – NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O)2R ^b , –NR ^d S(=O)2NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , – OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O)2R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O)2R ^c , – OS(=O)2OR ^c , –S(=O)NR ^d R ^e , –OS(=O)2NR ^d R ^e , and –S(=O)2NR ^d R ^e , where said C1-6 alkyl, O- C1-6 alkyl, C3-6 cycloalkyl, and 3-7 membered heterocycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl and O-C1-6 alkyl; or R ¹ is absent and R ² combines with the nitrogen to which it is attached to form an imino group of formula =CR ^w R ^x , an amidine of formula =C(R ^w )(NR ^y R ^z ), or a guanidine of formula =C(NR ^y R ^z )2 where R ^w , R ^x are independently C1-6 alkyl and R ^y and R ^z are independently selected from hydrogen and C1-6 alkyl; or R ¹ and R ² together with the nitrogen atom to which they are attached form a 3-15 membered heterocycloalkyl ring or 4-15 membered heteroaryl ring, each independently and optionally containing one or more further heteroatoms selected from O, N, and S and wherein each ring is independently and optionally substituted with one or more R ^a3 ; where each R ^a3 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1- ₆ haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-15 membered heterocycloalkyl, 4-15 membered heteroaryl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , –NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O) ₂ R ^b , –NR ^d S(=O) ₂ NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , –OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O) ₂ R ^c , –S(=O)R ^c , –OS(=O)R ^c , – OS(=O) ₂ R ^c , –OS(=O) ₂ OR ^c , –S(=O)NR ^d R ^e , –OS(=O) ₂ NR ^d R ^e , and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-15 membered heterocycloalkyl, and 4-15 membered heteroaryl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl; R is selected from the group consisting of C _1-10 alkyl optionally substituted by one or more R ^a , C _2-10 alkenyl optionally substituted by one or more R ^a , C _2-6 alkynyl optionally substituted by one or more R ^a , C _6-15 aryl optionally substituted by one or more R ^a , C _6-15 aryl(C _{1- 6} )alkyl optionally substituted by one or more R ^a , C _3-11 cycloalkyl optionally substituted by one or more R ^a , C _3-11 cycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a , 4-15 membered heterocycloalkyl(C _{1- 6} )alkyl optionally substituted by one or more R ^a , 4-15 membered heteroaryl optionally substituted by one or more R ^a , and 4-15 membered heteroaryl(C _1-6 )alkyl optionally substituted by one or more R ^a ; where each R ^a is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, C6-11 aryl, – C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , – NR ^d C(=O)OR ^c , –NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O)2R ^b , –NR ^d S(=O)2NR ^d R ^e , –OR ^c , –SR ^c , – OC(=O)R ^b , –OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O)2R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O)2R ^c , –OS(=O)2OR ^c , –S(=O)NR ^d R ^e , –OS(=O)2NR ^d R ^e , and –S(=O)2NR ^d R ^e , where said C1-6 alkyl, O- C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl and C6-11 aryl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl; R ³ is selected from the group consisting of H, C1-6 alkyl, CN, –C(=O)R ^f , –C(=O)OR ^g , – C(=O)NR ^h R ^j , –C(O)C(=O)R ^f , –NR ^h R ^j , –NR ^g C(=O)R ^f , –NR ^h C(=O)OR ^g , –NR ^h C(=O)NR ^h R ^j , – NR ^h S(=O)2R ^f , –NR ^h S(=O)2NR ^h R ^j , –OR ^g , –SR ^g , –OC(=O)R ^f , –OC(=O)NR ^h R ^j , –OC(=O)OR ^g , – S(=O)2R ^g , –S(=O)R ^g , –OS(=O)R ^g , –OS(=O)2R ^g , –OS(=O)2OR ^g , –S(=O)NR ^h R ^j , – OS(=O)2NR ^h R ^j , and –S(=O)2NR ^h R ^j , where said C1-6 alkyl is optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl; R ⁴ is selected from the group consisting of hydrogen, C _1-10 alkyl optionally substituted by one or more R ^a4 , C _2-10 alkenyl optionally substituted by one or more R ^a4 , C _2-6 alkynyl optionally substituted by one or more R ^a4 , C _6-15 aryl optionally substituted by one or more R ^a4 , C _6-15 aryl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , C _3-11 cycloalkyl optionally substituted by one or more R ^a4 , C _3-11 cycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a4 , 4-15 membered heterocycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , 4-15 membered heteroaryl optionally substituted by one or more R ^a4 , and 4-15 membered heteroaryl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , CN, –C(=O)R ^f , –C(=O)OR ^g , – C(=O)NR ^h R ^j , –C(O)C(=O)R ^f , –OR ^g , –SR ^g , –OC(=O)R ^f , –OC(=O)NR ^h R ^j , –OC(=O)OR ^g , – S(=O) ₂ R ^g , –S(=O)R ^g , –OS(=O)R ^g , –OS(=O) ₂ R ^g , –OS(=O) ₂ OR ^g , –S(=O)NR ^h R ^j , – OS(=O) ₂ NR ^h R ^j , and –S(=O) ₂ NR ^h R ^j ; where each R ^a4 is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _{1- 6} haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , – NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O) ₂ R ^b , –NR ^d S(=O) ₂ NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , – OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O)2R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O)2R ^c , – OS(=O)2OR ^c , –S(=O)NR ^d R ^e , –OS(=O)2NR ^d R ^e , and –S(=O)2NR ^d R ^e , where said C1-6 alkyl, O- C1-6 alkyl, C3-6 cycloalkyl, and 3-7 membered heterocycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl and O-C1-6 alkyl; wherein each R ^b and R ^f are independently selected from hydrogen, hydroxyl, halogen, CN, C1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, C6-15 aryl, C6-15aryl(C1-6)alkyl, C3-11cycloalkyl(C1-6)alkyl, 4-15 membered heterocycloalkyl(C1-6)alkyl, and 4-15 membered heteroaryl(C1-6)alkyl, wherein said C1-6 alkyl, C6-15 aryl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C6- 15aryl(C1-6)alkyl, C3-11cycloalkyl(C1-6)alkyl, 4-15 membered heterocycloalkyl(C1-6)alkyl, and 4- 15 membered heteroaryl(C1-6)alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO2, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl; wherein each R ^c and R ^g are independently selected from hydrogen, hydroxyl, halogen, CN, C1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, O-C _1-6 alkyl and C _6-15 aryl, wherein said C _1-6 alkyl, C _6-15 aryl, 3-7 membered heterocycloalkyl 5-6 membered heteroaryl and C _3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, nitro, amino, C _1-6 haloalkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl; wherein each R ^d and R ^h are independently selected from hydrogen, hydroxyl, halogen, CN, C _1-6 haloalkyl, C _3-6 cycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl; wherein each R ^e and R ^j are independently selected from hydrogen, hydroxyl, halogen, CN, C _1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, C _6-15 aryl, C _6-15 aryl(C _1-6 )alkyl, C _3-11 cycloalkyl(C _1-6 )alkyl, 4-15 membered heterocycloalkyl(C _1-6 )alkyl, and 4-15 membered heteroaryl(C _1-6 )alkyl, wherein said C _1-6 alkyl, C _6-15 aryl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C _3-6 cycloalkyl, C _{6- 15} aryl(C _1-6 )alkyl, C _3-11 cycloalkyl(C _1-6 )alkyl, 4-15 membered heterocycloalkyl(C _1-6 )alkyl, and 4- 15 membered heteroaryl(C _1-6 )alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO ₂ , C _1-6 haloalkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl; or wherein R ^d and R ^e , when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more for heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more R ^k ; wherein R ^h and R ^j , when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more for heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more R ^k ; and where R ^k is selected from hydrogen, =O, halogen, CN, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl and O-C1-6 alkyl. 2. A process according to paragraph 1 wherein P ² is selected from tert-octyl, tert-butyl, TIPS, TBDMS, TBDPS and TMS. 3. A process according to paragraph 1 or 2, wherein P ² is selected from tert-octyl and TIPS, suitably tert-octyl. 4. A process according to any one of the preceding paragraphs wherein P ³ is selected from nosyl, tosyl, brosyl, mesyl, 2-(Trimethylsilyl)ethanesulfonyl (SES), and tert-Butylsulfonyl (Bus). 5. A process according to any one of the preceding paragraphs wherein P ³ is selected from nosyl and tosyl, suitably nosyl. 6. A process according to any one of the preceding paragraphs wherein P ² is selected from tert-octyl and tert-butyl, and the deprotection of the compound of formula II is carried out by treatment with acid. 7. A process according to paragraph 7, wherein the acid is selected from TFA, MsOH and TfOH, suitably, the acid is TFA. 8. A process according to any one of paragraph 1 to 5 wherein P ² is Si(R ₅ ) ₃ and a source of fluoride is used in the deprotection of the compound of formula II to give a compound of formula Ia. Suitably, the source of fluoride is selected from TBAF, cesium fluoride, potassium fluoride, and HF. 9. A process according to any one of the preceding paragraphs wherein the reactant suitable for introducing group R ³ is R ³ -X ² wherein X ² is a leaving group. Suitably, X ² is halo, for instance Cl or Br. 10. A process according to any one of the preceding paragraphs wherein the reactant suitable for introducing group R ³ is (i) R ^j -N=C=O, when R ³ is –C(=O)NR ^h R ^j , and R ^h is H, or (ii) R ³ -CHO, when R ³ is C _1-6 alkyl. 11. A process according to any one of the preceding paragraphs, wherein P ³ is a nosyl group and the deprotection of formula Ib to give a compound according to formula Ic is performed using a thiolate nucleophile. Suitable thiolate nucleophiles are, for example, thiophenol, thioglycolic acid, C1-20alkyl-SH. 12. A process according to paragraph 11, wherein the removal of the nosyl is carried out in the presence of a base, such a carbonate or hydroxide base, or a non-nucleophilic base such as DBU. 13. A process according to any one of the preceding paragraphs wherein P ³ is nosyl and the deprotection of formula Ib to give a compound according to formula Ic is performed using C12alkyl-SH and DBU. Suitably, in acetonitrile at about 0°C. 14. A process according to any one paragraphs 1 to 10, wherein P ³ is nosyl and the and the deprotection of formula Ib to give a compound according to formula Ic is performed using a reducing agent, such as sodium amalgam (Na(Hg)), aluminium amalgam, magnesium, samarium(II) iodide), tin hydrides (tributyltin hydride) and transition metal complexes with reducing agents. 15. A process according to any one of paragraphs 1 to 10, wherein P ³ is SES and the deprotection of formula Ib to give a compound according to formula Ic is performed using a source of fluoride. Suitably, the source of fluoride is selected from TBAF, cesium fluoride, potassium fluoride and HF. 16. A process according to any one of paragraphs 1 to 10, wherein P ³ is Bus, tosyl, brosyl and mesyl and the deprotection of formula Ib to give a compound according to formula Ic is performed using an acid. Suitably, the acid is selected from TFA, MsOH, TfOH. Suitably, the acid is TFA. 17. A process according to any one of the preceding paragraphs, wherein the reactant suitable for introducing group R ⁴ is selected from: (i) R ⁴ -B ¹ when R ⁴ is C _6-15 aryl optionally substituted by one or more R ^a4 or 4-15 membered heteroaryl optionally substituted by one or more R ^a4 , and wherein B ¹ is a boronic acid, a boronic acid ester, a cyclic boronic acid ester, an organotrifluoroborate potassium salt, cyclic triolborate, organoborane, or MIDA boronate; (ii) X ³ -C(=O)OR ^g when R ⁴ is –C(=O)OR ^g , wherein X ³ is a leaving group, suitably halo, for instance Cl, Br or I; (iii) R ⁴ -X ⁴ when R ⁴ is C1-10alkyl optionally substituted by one or more R ^a4 , C2-10alkenyl optionally substituted by one or more R ^a4 , C2-6alkynyl optionally substituted by one or more R ^a4 , C6-15aryl optionally substituted by one or more R ^a4 , 4-15 membered heteroaryl optionally substituted by one or more R ^a4 , C6-15aryl(C1-6)alkyl optionally substituted by one or more R ^a4 , C(=O)NR ^h R ^j , and –C(=O)R ^f , and wherein X ⁴ is a leaving group, suitably halo, for instance Cl, Br or I. (iv) TMS-R ⁴ when R ⁴ is CF3 and CN. 18. A process according to any one of the preceding paragraphs wherein, the process further comprises preparing a compound of formula II (II), comprising reacting a compound of formula (III): (III), with a compound of formula (IV): H-NR1R2 (IV); wherein X is a leaving group; and R, R ¹ , R ² , P ² and P ³ are as defined in any one of paragraphs 1 to 6. 19. A process according to paragraph 18, wherein X is halo, suitably F. 20. A process according to paragraph 18, wherein X is imidazole or triazole. 21. A process according to any one of paragraphs 18 to 20, wherein the reaction between formula III and formula IV is conducted in the presence of a Lewis acid. Suitably, the Lewis acid is a triflimide salt. In particular a triflimide salt selected from Ca(NTf)2 or Ba(NTf)2. 22. A process according to paragraph 21, wherein the reaction between formula III and formula IV is conducted in the presence of a Lewis acid in a protic solvent, such as an alcohol or water. Suitably, the alcohol is a C3-C6 alcohol, suitably t-amyl alcohol or t-butanol. 23. A process according to any one of paragraphs 18 to 22, wherein the reaction between formula III and formula IV is additionally conducted in the presence of a base. Suitable bases are, for instance, DABCO or DIPEA. 24. A process according to paragraph 23, wherein the reaction is between formula III and formula IV is conducted in the presence of a Lewis acid and a base, suitably Ca(NTf)2 and DABCO. 25. A process according to any one of paragraphs 18 to 20, wherein the reaction between formula III and formula IV is conducted with a fluoride scavenger and a catalyst. Suitably, the fluoride scavenger is a silicon compound, such as a silane or siloxane. Suitable silicon compounds are, for instance, 1,1,3,3-tetramethyldisiloxane (TMDS), polymethylhydrosiloxane (PMHS), and (EtO)2MeSiH. 26. A process according to paragraph 26, wherein the catalyst is hydroxybenzotriazole (HOBt). 27. A process according to any one of paragraphs 25 and 26, wherein the reaction between formula III and formula IV is conducted with HOBt and TMDS. 28. A process according to any one of the preceding paragraphs, wherein the process further comprises preparing a compound of formula III: (III), comprising reaction a compound of formula V: (V), with a halogenating agent; wherein R, P ² and P ³ are as defined in any one of paragraphs 1 to 6. 29. A process according to paragraph 28, wherein X is F and the halogenating agent is a fluorinating agent. Suitably, the fluorinating agent is selected from N- fluorobenzenesulfonimide (NFSI), N-fluoro-o-benzenedisulfonimide (NFOBS) and Selectfluor. 30. A process according to any one of the preceding paragraphs, wherein the process further comprises preparing a compound of formula V: (V), comprising protecting a compound of formula VI: (VI), with a nitrogen protecting group P ³ ; wherein R, P ² and P ³ are as defined any one of paragraphs 1 to 6. 31. A process according to paragraph 30, wherein the compound VI is protected by reacting with R ⁶ SO2X ⁵ , wherein X ⁵ is a leaving group, suitably halo, for instance Cl, Br or I. 32. A process according to paragraph 31, wherein the reaction is conducted in the presence of a base, for instance triethylamine or DIPEA. 33. A process according to any one of paragraphs 30 to 32, wherein P ³ is nosyl and the compound of formula VI is protected by reaction with NsCl. 34. A process according to any one of the preceding paragraphs, wherein the process further comprises preparing a compound of formula VI: (VI), comprising reacting a compound of formula VII: with an organometallic reactant compound of formula VIII: R-M (VIII) wherein P ¹ is a nitrogen protecting group selected from a group of formula Si(R ⁷ ) 7 3 wherein R is independently selected from C1-4 alkyl and a phenyl group; M is a metallic moiety; and R and P ² are as defined in any one of paragraphs 1 to 6. 35. A process according to paragraph 34, wherein the metallic moiety of formula VIII is lithium. 36. A process according to paragraph 34, wherein the metallic moiety of formula VIII is MgX ⁶ , wherein X ⁶ is halo, suitably Cl, Br or I, more suitably Cl or Br. 37. A process according to any one of paragraphs 34 to 36, wherein R ⁷ is selected from methyl, ethyl or isopropyl. Suitably, each R ⁷ is methyl (i.e. P ¹ is TMS). 38. A process according to any one of paragraphs 34 to 37, wherein P ¹ is TMS or TIPS, suitably TMS. 39. A process according to any one of the preceding paragraphs, wherein the process further comprises preparing a compound of formula VII: from a compound of formula IX: 40. A process according to paragraph 39, wherein formula VII is prepared from formula IX by reacting formula IX with P ¹ -X ⁷ and a base, wherein X ⁷ is halo, suitably Cl or Br. 41. A process according to any one of paragraphs 39 and 40, wherein P ¹ is TMS and formula VII is prepared from formula IX by reacting formula IX with LiHMDS and TMSCl. 42. A process according to any one of the preceding paragraphs, wherein the compound of formula VI is not isolated prior to the following step. 43. A process according to any one of the preceding paragraphs, wherein the compound of formula VII is not isolated prior to the following step. 44. A process for the preparation of a compound of formula II, or a salt thereof: comprising reacting a compound of formula III: (III), with a compound of formula (IV): H-NR1R2 (IV), wherein R, R ¹ , R ² , P ² and P ³ are as defined in any one of paragraphs 1 to 6 and X is a leaving group. 45. A process according to paragraph 44, wherein X is halo, suitably F. 46. A process according to paragraph 44, wherein X is imidazole or triazole. 47. A process according to any one of paragraphs 44 to 46, wherein the reaction between formula III and formula IV is conducted in the presence of a Lewis acid. Suitably, the Lewis acid is a triflimide salt. In particular a triflimide salt selected from Ca(NTf) ₂ or Ba(NTf) ₂ . 48. A process according to paragraph 47, wherein the reaction between formula III and formula IV is conducted in the presence of a Lewis acid in a protic solvent, such as an alcohol or water. Suitably, the alcohol is a C3-C6 alcohol, suitably t-amyl alcohol or t-butanol. 49. A process according to any one of paragraphs 44 to 48, wherein the reaction between formula III and formula IV is additionally conducted in the presence of a base. Suitable bases are, for instance, DABCO or DIPEA. 50. A process according to paragraph 49, wherein the reaction is between formula III and formula IV is conducted in the presence of a Lewis acid and a base, suitably Ca(NTf)2 and DABCO. 51. A process according to any one of paragraphs 44 to 46, wherein the reaction between formula III and formula IV is conducted with a fluoride scavenger and a catalyst. Suitably, the fluoride scavenger is a silicon compound, such as a silane or siloxane. Suitable silicon compounds are, for instance, 1,1,3,3-tetramethyldisiloxane (TMDS), polymethylhydrosiloxane (PMHS), and (EtO)2MeSiH. 52. A process according to paragraph 51, wherein the catalyst is hydroxybenzotriazole (HOBt). 53. A process according to any one of paragraphs 51 and 52, wherein the reaction between formula III and formula IV is conducted with HOBt and TMDS. 54. A process according to any one of paragraphs 44 to 53, wherein the process further comprises preparing a compound of formula III: (III), comprising reaction a compound of formula V: (V), with a halogenating agent; wherein R, P ² and P ³ are as defined in any one of paragraphs 1 to 6. 55. A process according to paragraph 54, wherein X is F and the halogenating agent is a fluorinating agent. Suitably, the fluorinating agent is selected from N- fluorobenzenesulfonimide (NFSI), N-fluoro-o-benzenedisulfonimide (NFOBS) and Selectfluor. 56. A process according to any one of paragraphs 44 to 55, wherein the process further comprises preparing a compound of formula V: (V), comprising protecting a compound of formula VI: (VI), with a nitrogen protecting group P ³ ; wherein R, P ² and P ³ are as defined any one of paragraphs 1 to 6. 57. A process according to paragraph 56, wherein the compound VI is protected by reacting with R ⁶ SO ₂ X ⁵ , wherein X ⁵ is a leaving group, suitably halo, for instance Cl, Br or I. 58. A process according to paragraph 57, wherein the reaction is conducted in the presence of a base, for instance triethylamine or DIPEA. 59. A process according to any one of paragraphs 56 to 58, wherein P ³ is nosyl and the compound of formula VI is protected by reaction with NsCl. 60. A process according to any one of paragraphs 44 to 59, wherein the process further comprises preparing a compound of formula VI: (VI), comprising reacting a compound of formula VII: with an organometallic reactant compound of formula VIII: R-M (VIII) wherein P ¹ is a nitrogen protecting group selected from a group of formula Si(R ⁷ ) ₃ wherein R7 is independently selected from C _1-4 alkyl and a phenyl group; M is a metallic moiety; and R and P ² are as defined in any one of paragraphs 1 to 6. 61. A process according to paragraph 60, wherein the metallic moiety of formula VIII is lithium. 62. A process according to paragraph 60, wherein the metallic moiety of formula VIII is MgX ⁶ , wherein X ⁶ is halo, suitably Cl, Br or I, more suitably Cl or Br. 63. A process according to any one of paragraphs 60 to 62, wherein R ⁷ is selected from methyl, ethyl or isopropyl. Suitably, each R ⁷ is methyl (i.e. P ¹ is TMS). 64. A process according to any one of paragraphs 60 to 63, wherein P ¹ is TMS or TIPS, suitably TMS. 65. A process according to any one of paragraphs 44 to 64, wherein the process further comprises preparing a compound of formula VII: from a compound of formula IX: 66. A process according to paragraph 65, wherein formula VII is prepared from formula IX by reacting formula IX with P ¹ -X ⁷ and a base, wherein X ⁷ is halo, suitably Cl or Br. 67. A process according to paragraph 65 and 66, wherein P ¹ is TMS and formula VII is prepared from formula IX by reacting formula IX with LiHMDS and TMSCl. 68. A process according to any one of paragraphs 44 to 67, wherein the compound of formula VI is not isolated prior to the following step. 69. A process according to any one of paragraphs 44 to 67, wherein the compound of formula VII is not isolated prior to the following step. 70. A process for the preparation of a compound of formula III, or a salt thereof: (III), comprising reaction a compound of formula V: with a halogenating agent; wherein R, P ² and P ³ are as defined in any of paragraphs 1 to 6, and X is a leaving group. 71. A process according to claim 70, wherein X is F and the halogenating agent is a fluorinating agent. Suitably, the fluorinating agent is selected from N- fluorobenzenesulfonimide (NFSI), N-fluoro-o-benzenedisulfonimide (NFOBS) and Selectfluor. 72. A process according to paragraphs 70 or 71, wherein the process further comprises preparing a compound of formula V: (V), comprising protecting a compound of formula VI: (VI), with a nitrogen protecting group P ³ . 73. A process according to paragraph 72, wherein the compound VI is protected by reacting with R ⁶ SO ₂ X ⁵ , wherein X ⁵ is a leaving group, suitably halo, for instance Cl, Br or I. 74. A process according to paragraph 73, wherein the reaction is conducted in the presence of a base, for instance triethylamine or DIPEA. 75. A process according to any one of paragraphs 72 to 74, wherein P ³ is nosyl and the compound of formula VI is protected by reaction with NsCl. 76. A process according to any one of paragraphs 70 to 75, wherein the process further comprises preparing a compound of formula VI: (VI), comprising reacting a compound of formula VII: (VII) with an organometallic reactant compound of formula VIII: R-M (VIII) wherein P ¹ is a nitrogen protecting group selected from a group of formula Si(R ⁷ ) ₃ wherein R7 is independently selected from C _1-4 alkyl and a phenyl group; M is a metallic moiety. 77. A process according to paragraph 76, wherein the metallic moiety of formula VIII is lithium. 78. A process according to paragraph 76, wherein the metallic moiety of formula VIII is MgX ⁶ , wherein X ⁶ is halo, suitably Cl, Br or I, more suitably Cl or Br. 79. A process according to any one of paragraphs 76 to 78, wherein R ⁷ is selected from methyl, ethyl or isopropyl. Suitably, each R ⁷ is methyl (i.e. P ¹ is TMS). 80. A process according to any one of paragraphs 76 to 79, wherein P ¹ is TMS or TIPS, suitably TMS. 81. A process according to any one of paragraphs 70 to 80, wherein the process further comprises preparing a compound of formula VII: from a compound of formula IX: 82. A process according to paragraph 81, wherein formula VII is prepared from formula IX by reacting formula IX with P ¹ -X ⁷ and a base, wherein X ⁷ is halo, suitably Cl or Br. 83. A process according to paragraph 81 and 82, wherein P ¹ is TMS and formula VII is prepared from formula IX by reacting formula IX with LiHMDS and TMSCl. 84. A process according to any one of paragraphs 70 to 83, wherein the compound of formula VI is not isolated prior to the following step. 85. A process according to any one of paragraphs 70 to 84, wherein the compound of formula VII is not isolated prior to the following step. 86. A process for the preparation of a compound of formula V, or a salt thereof: (V), comprising protecting a compound of formula VI: (VI), with a nitrogen protecting group P ³ ; wherein R, P ² and P ³ are as defined any one of paragraphs 1 to 6. 87. A process according to paragraph 86, wherein the compound VI is protected by reacting with R ⁶ SO ₂ X ⁵ , wherein X ⁵ is a leaving group, suitably halo, for instance Cl, Br or I. 88. A process according to paragraph 87, wherein the reaction is conducted in the presence of a base, for instance triethylamine or DIPEA. 89. A process according to any one of paragraphs 86 to 88, wherein P ³ is nosyl and the compound of formula VI is protected by reaction with NsCl. 90. A process according to any one of paragraphs 86 to 89, wherein the process further comprises preparing a compound of formula VI: (VI), comprising reacting a compound of formula VII: with an organometallic reactant compound of formula VIII: R-M (VIII) wherein P ¹ is a nitrogen protecting group selected from a group of formula Si(R ⁷ ) 7 3 wherein R is independently selected from C1-4 alkyl and a phenyl group; M is a metallic moiety. 91. A process according to paragraph 90, wherein the metallic moiety of formula VIII is lithium. 92. A process according to paragraph 90, wherein the metallic moiety of formula VIII is MgX ⁶ , wherein X ⁶ is halo, suitably Cl, Br or I, more suitably Cl or Br. 93. A process according to any one of paragraphs 90 to 92, wherein R ⁷ is selected from methyl, ethyl or isopropyl. Suitably, each R ⁷ is methyl (i.e. P ¹ is TMS). 94. A process according to any one of paragraphs 90 to 93, wherein P ¹ is TMS or TIPS, suitably TMS. 95. A process according to any one of paragraphs 86 to 94, wherein the process further comprises preparing a compound of formula VII: from a compound of formula IX: 96. A process according to paragraph 95, wherein formula VII is prepared from formula IX by reacting formula IX with P ¹ -X ⁷ and a base, wherein X ⁷ is halo, suitably Cl or Br. 97. A process according to paragraph 95 and 96, wherein P ¹ is TMS and formula VII is prepared from formula IX by reacting formula IX with LiHMDS and TMSCl. 98. A process according to any one of paragraphs 86 to 97, wherein the compound of formula VI is not isolated prior to the following step. 99. A process according to any one of paragraphs 86 to 98, wherein the compound of formula VII is not isolated prior to the following step. 100. A process for the preparation of a compound of formula VI: (VI), comprising reacting a compound of formula VII: with a compound of formula VIII: R-M (VIII); wherein R and P ² are as defined in any one of paragraphs 1 to 6; P ¹ is a nitrogen protecting group selected from a group of formula Si(R ⁷ )3 wherein R ⁷ is independently selected from C _1-4 alkyl and a phenyl group; and M is a metallic moiety. 101. A process according to paragraph 100, wherein the metallic moiety of formula VIII is lithium. 102. A process according to paragraph 100, wherein the metallic moiety of formula VIII is MgX ⁶ , wherein X ⁶ is halo, suitably Cl, Br or I, more suitably Cl or Br. 103. A process according to any one of paragraphs 100 to 102, wherein R ⁷ is selected from methyl, ethyl or isopropyl. Suitably, each R ⁷ is methyl (i.e. P ¹ is TMS). 104. A process according to any one of paragraphs 100 to 103, wherein P ¹ is TMS or TIPS, suitably TMS. 105. A process according to any one of paragraphs 100 to 104, wherein the process further comprises preparing a compound of formula VII: from a compound of formula IX: 106. A process according to paragraph 105, wherein formula VII is prepared from formula IX by reacting formula IX with P ¹ -X ⁷ and a base, wherein X ⁷ is halo, suitably Cl or Br. 107. A process according to paragraph 105 and 106, wherein P ¹ is TMS and formula VII is prepared from formula IX by reacting formula IX with LiHMDS and TMSCl. 108. A process according to any one of paragraphs 100 to 107, wherein the compound of formula VI is not isolated prior to the following step. 109. A process according to any one of paragraphs 100 to 108, wherein the compound of formula VII is not isolated prior to the following step. 110. A compound of formula I, or a salt thereof: (I), wherein, R ¹ is selected from the group consisting of hydrogen, C1-10alkyl optionally substituted by one or more R ^a1 , C2-10alkenyl optionally substituted by one or more R ^a1 , C2-6alkynyl optionally substituted by one or more R ^a1 , C6-15aryl optionally substituted by one or more R ^a1 , C6-15aryl(C1-6)alkyl optionally substituted by one or more R ^a1 , C3-11cycloalkyl optionally substituted by one or more R ^a1 , C3-11cycloalkyl(C1-6)alkyl optionally substituted by one or more R ^a1 , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a1 , 4-15 membered heterocycloalkyl(C1-6)alkyl optionally substituted by one or more R ^a1 , 4-15 membered heteroaryl optionally substituted by one or more R ^a1 , and 4-15 membered heteroaryl(C1-6)alkyl optionally substituted by one or more R ^a1 , –C(=O)R ^b , –C(=O)OR ^c , – C(=O)NR ^d R ^e , and –C(O)C(=O)R ^b ; where each R ^a1 is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _{1- 6} haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , – NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O) ₂ R ^b , –NR ^d S(=O) ₂ NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , – OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O) ₂ R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O) ₂ R ^c , – OS(=O) ₂ OR ^c , –S(=O)NR ^d R ^e , –OS(=O) ₂ NR ^d R ^e , and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O- C _1-6 alkyl, C _3-6 cycloalkyl, and 3-7 membered heterocycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl; R ² is selected from the group consisting of hydrogen, C _1-10 alkyl optionally substituted by one or more R ^a2 , C _2-10 alkenyl optionally substituted by one or more R ^a2 , C _2-6 alkynyl optionally substituted by one or more R ^a2 , C _6-15 aryl optionally substituted by one or more R ^a2 , C _6-15 aryl(C _1-6 )alkyl optionally substituted by one or more R ^a2 , C _3-11 cycloalkyl optionally substituted by one or more R ^a2 , C _3-11 cycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a2 , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a2 , 4-15 membered heterocycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a2 , 4-15 membered heteroaryl optionally substituted by one or more R ^a2 , and 4-15 membered heteroaryl(C1-6)alkyl optionally substituted by one or more R ^a2 , –C(=O)R ^b , –C(=O)OR ^c , – C(=O)NR ^d R ^e , and –C(O)C(=O)R ^b ; where each R ^a2 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1- 6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , – NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O)2R ^b , –NR ^d S(=O)2NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , – OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O)2R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O)2R ^c , – OS(=O)2OR ^c , –S(=O)NR ^d R ^e , –OS(=O)2NR ^d R ^e , and –S(=O)2NR ^d R ^e , where said C1-6 alkyl, O- C1-6 alkyl, C3-6 cycloalkyl, and 3-7 membered heterocycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl and O-C1-6 alkyl; or R ¹ is absent and R ² combines with the nitrogen to which it is attached to form an imino group of formula =CR ^w R ^x , an amidine of formula =C(R ^w )(NR ^y R ^z ), or a guanidine of formula =C(NR ^y R ^z )2 where R ^w , R ^x are independently C1-6 alkyl and R ^y and R ^z are independently selected from hydrogen and C1-6 alkyl; or R ¹ and R ² together with the nitrogen atom to which they are attached form a 3-15 membered heterocycloalkyl ring or 4-15 membered heteroaryl ring, each independently and optionally containing one or more further heteroatoms selected from O, N, and S and wherein each ring is independently and optionally substituted with one or more R ^a3 ; where each R ^a3 is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _{1- 6} haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-15 membered heterocycloalkyl, 4-15 membered heteroaryl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , –NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O) ₂ R ^b , –NR ^d S(=O) ₂ NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , –OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O) ₂ R ^c , –S(=O)R ^c , –OS(=O)R ^c , – OS(=O) ₂ R ^c , –OS(=O) ₂ OR ^c , –S(=O)NR ^d R ^e , –OS(=O) ₂ NR ^d R ^e , and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-15 membered heterocycloalkyl, and 4-15 membered heteroaryl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl; R is selected from the group consisting of C _1-10 alkyl optionally substituted by one or more R ^a , C _2-10 alkenyl optionally substituted by one or more R ^a , C _2-6 alkynyl optionally substituted by one or more R ^a , C _6-15 aryl optionally substituted by one or more R ^a , C _6-15 aryl(C _{1- 6} )alkyl optionally substituted by one or more R ^a , C _3-11 cycloalkyl optionally substituted by one or more R ^a , C _3-11 cycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a , 4-15 membered heterocycloalkyl(C1- 6)alkyl optionally substituted by one or more R ^a , 4-15 membered heteroaryl optionally substituted by one or more R ^a , and 4-15 membered heteroaryl(C1-6)alkyl optionally substituted by one or more R ^a ; where each R ^a is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, C6-11 aryl, – C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , – NR ^d C(=O)OR ^c , –NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O)2R ^b , –NR ^d S(=O)2NR ^d R ^e , –OR ^c , –SR ^c , – OC(=O)R ^b , –OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O)2R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O)2R ^c , –OS(=O)2OR ^c , –S(=O)NR ^d R ^e , –OS(=O)2NR ^d R ^e , and –S(=O)2NR ^d R ^e , where said C1-6 alkyl, O- C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl and C6-11 aryl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl; R ³ is selected from the group consisting of H, C1-6 alkyl, CN, –C(=O)R ^f , –C(=O)OR ^g , – C(=O)NR ^h R ^j , –C(O)C(=O)R ^f , –NR ^h R ^j , –NR ^g C(=O)R ^f , –NR ^h C(=O)OR ^g , –NR ^h C(=O)NR ^h R ^j , – NR ^h S(=O) ₂ R ^f , –NR ^h S(=O) ₂ NR ^h R ^j , –OR ^g , –SR ^g , –OC(=O)R ^f , –OC(=O)NR ^h R ^j , –OC(=O)OR ^g , – S(=O) ₂ R ^g , –S(=O)R ^g , –OS(=O)R ^g , –OS(=O) ₂ R ^g , –OS(=O) ₂ OR ^g , –S(=O)NR ^h R ^j , – OS(=O) ₂ NR ^h R ^j , and –S(=O) ₂ NR ^h R ^j , where said C _1-6 alkyl is optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl; R ⁴ is selected from the group consisting of hydrogen, C _1-10 alkyl optionally substituted by one or more R ^a4 , C _2-10 alkenyl optionally substituted by one or more R ^a4 , C _2-6 alkynyl optionally substituted by one or more R ^a4 , C _6-15 aryl optionally substituted by one or more R ^a4 , C _6-15 aryl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , C _3-11 cycloalkyl optionally substituted by one or more R ^a4 , C _3-11 cycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a4 , 4-15 membered heterocycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , 4-15 membered heteroaryl optionally substituted by one or more R ^a4 , and 4-15 membered heteroaryl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , CN, –C(=O)R ^f , –C(=O)OR ^g , – C(=O)NR ^h R ^j , –C(O)C(=O)R ^f , –OR ^g , –SR ^g , –OC(=O)R ^f , –OC(=O)NR ^h R ^j , –OC(=O)OR ^g , – S(=O) ₂ R ^g , –S(=O)R ^g , –OS(=O)R ^g , –OS(=O) ₂ R ^g , –OS(=O) ₂ OR ^g , –S(=O)NR ^h R ^j , – OS(=O) ₂ NR ^h R ^j , and –S(=O) ₂ NR ^h R ^j ; where each R ^a4 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1- 6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , – NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O)2R ^b , –NR ^d S(=O)2NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , – OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O)2R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O)2R ^c , – OS(=O)2OR ^c , –S(=O)NR ^d R ^e , –OS(=O)2NR ^d R ^e , and –S(=O)2NR ^d R ^e , where said C1-6 alkyl, O- C1-6 alkyl, C3-6 cycloalkyl, and 3-7 membered heterocycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl and O-C1-6 alkyl; wherein each R ^b and R ^f are independently selected from hydrogen, hydroxyl, halogen, CN, C1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, C6-15 aryl, C6-15aryl(C1-6)alkyl, C3-11cycloalkyl(C1-6)alkyl, 4-15 membered heterocycloalkyl(C1-6)alkyl, and 4-15 membered heteroaryl(C1-6)alkyl, wherein said C1-6 alkyl, C6-15 aryl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C6- 15aryl(C1-6)alkyl, C3-11cycloalkyl(C1-6)alkyl, 4-15 membered heterocycloalkyl(C1-6)alkyl, and 4- 15 membered heteroaryl(C1-6)alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO2, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl; wherein each R ^c and R ^g are independently selected from hydrogen, hydroxyl, halogen, CN, C _1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl and C _6-15 aryl, wherein said C _1-6 alkyl, C _6-15 aryl, 3-7 membered heterocycloalkyl 5-6 membered heteroaryl and C _3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, nitro, amino, C _1-6 haloalkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl; wherein each R ^d and R ^h are independently selected from hydrogen, hydroxyl, halogen, CN, C _1-6 haloalkyl, C _3-6 cycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl; wherein each R ^e and R ^j are independently selected from hydrogen, hydroxyl, halogen, CN, C _1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, C _6-15 aryl, C _6-15 aryl(C _1-6 )alkyl, C _3-11 cycloalkyl(C _1-6 )alkyl, 4-15 membered heterocycloalkyl(C _1-6 )alkyl, and 4-15 membered heteroaryl(C _1-6 )alkyl, wherein said C _1-6 alkyl, C _6-15 aryl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C _3-6 cycloalkyl, C _{6- 15} aryl(C _1-6 )alkyl, C _3-11 cycloalkyl(C _1-6 )alkyl, 4-15 membered heterocycloalkyl(C _1-6 )alkyl, and 4- 15 membered heteroaryl(C _1-6 )alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO ₂ , C _1-6 haloalkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl; or wherein R ^d and R ^e , when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more for heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more R ^k ; wherein R ^h and R ^j , when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more for heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more R ^k ; where R ^k is selected from hydrogen, =O, halogen, CN, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl and O-C1-6 alkyl; with the provisos that: (i) when R is methyl, ethyl or butyl then R ³ and R ⁴ cannot both be methyl; and (ii) when R is optionally substituted phenyl then R ³ and R ⁴ cannot both be -SO2CF3. 111. A compound of formula Ia, Ib or Ic: (Ia), (Ib), (Ic), wherein, R ¹ is selected from the group consisting of hydrogen, C _1-10 alkyl optionally substituted by one or more R ^a1 , C _2-10 alkenyl optionally substituted by one or more R ^a1 , C _2-6 alkynyl optionally substituted by one or more R ^a1 , C _6-15 aryl optionally substituted by one or more R ^a1 , C _6-15 aryl(C _1-6 )alkyl optionally substituted by one or more R ^a1 , C _3-11 cycloalkyl optionally substituted by one or more R ^a1 , C _3-11 cycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a1 , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a1 , 4-15 membered heterocycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a1 , 4-15 membered heteroaryl optionally substituted by one or more R ^a1 , and 4-15 membered heteroaryl(C1-6)alkyl optionally substituted by one or more R ^a1 , –C(=O)R ^b , –C(=O)OR ^c , – C(=O)NR ^d R ^e , and –C(O)C(=O)R ^b ; where each R ^a1 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1- 6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , – NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O)2R ^b , –NR ^d S(=O)2NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , – OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O)2R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O)2R ^c , – OS(=O)2OR ^c , –S(=O)NR ^d R ^e , –OS(=O)2NR ^d R ^e , and –S(=O)2NR ^d R ^e , where said C1-6 alkyl, O- C1-6 alkyl, C3-6 cycloalkyl, and 3-7 membered heterocycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl and O-C1-6 alkyl; R ² is selected from the group consisting of hydrogen, C1-10alkyl optionally substituted by one or more R ^a2 , C2-10alkenyl optionally substituted by one or more R ^a2 , C2-6alkynyl optionally substituted by one or more R ^a2 , C6-15aryl optionally substituted by one or more R ^a2 , C6-15aryl(C1-6)alkyl optionally substituted by one or more R ^a2 , C3-11cycloalkyl optionally substituted by one or more R ^a2 , C _3-11 cycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a2 , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a2 , 4-15 membered heterocycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a2 , 4-15 membered heteroaryl optionally substituted by one or more R ^a2 , and 4-15 membered heteroaryl(C _1-6 )alkyl optionally substituted by one or more R ^a2 , –C(=O)R ^b , –C(=O)OR ^c , – C(=O)NR ^d R ^e , and –C(O)C(=O)R ^b ; where each R ^a2 is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _{1- 6} haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , – NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O) ₂ R ^b , –NR ^d S(=O) ₂ NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , – OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O) ₂ R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O) ₂ R ^c , – OS(=O) ₂ OR ^c , –S(=O)NR ^d R ^e , –OS(=O) ₂ NR ^d R ^e , and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O- C _1-6 alkyl, C _3-6 cycloalkyl, and 3-7 membered heterocycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl; or R ¹ is absent and R ² combines with the nitrogen to which it is attached to form an imino group of formula =CR ^w R ^x , an amidine of formula =C(R ^w )(NR ^y R ^z ), or a guanidine of formula =C(NR ^y R ^z )2 where R ^w , R ^x are independently C1-6 alkyl and R ^y and R ^z are independently selected from hydrogen and C1-6 alkyl; or R ¹ and R ² together with the nitrogen atom to which they are attached form a 3-15 membered heterocycloalkyl ring or 4-15 membered heteroaryl ring, each independently and optionally containing one or more further heteroatoms selected from O, N, and S and wherein each ring is independently and optionally substituted with one or more R ^a3 ; where each R ^a3 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1- 6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, C6-11 aryl, 3-15 membered heterocycloalkyl, 4-15 membered heteroaryl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , –NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O)2R ^b , –NR ^d S(=O)2NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , –OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O)2R ^c , –S(=O)R ^c , –OS(=O)R ^c , – OS(=O)2R ^c , –OS(=O)2OR ^c , –S(=O)NR ^d R ^e , –OS(=O)2NR ^d R ^e , and –S(=O)2NR ^d R ^e , where said C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, C6-11 aryl, 3-15 membered heterocycloalkyl, and 4-15 membered heteroaryl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl; R is selected from the group consisting of C _1-10 alkyl optionally substituted by one or more R ^a , C _2-10 alkenyl optionally substituted by one or more R ^a , C _2-6 alkynyl optionally substituted by one or more R ^a , C _6-15 aryl optionally substituted by one or more R ^a , C _6-15 aryl(C _{1- 6} )alkyl optionally substituted by one or more R ^a , C _3-11 cycloalkyl optionally substituted by one or more R ^a , C _3-11 cycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a , 4-15 membered heterocycloalkyl(C _{1- 6} )alkyl optionally substituted by one or more R ^a , 4-15 membered heteroaryl optionally substituted by one or more R ^a , and 4-15 membered heteroaryl(C _1-6 )alkyl optionally substituted by one or more R ^a ; where each R ^a is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, C _6-11 aryl, – C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , – NR ^d C(=O)OR ^c , –NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O) ₂ R ^b , –NR ^d S(=O) ₂ NR ^d R ^e , –OR ^c , –SR ^c , – OC(=O)R ^b , –OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O) ₂ R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O) ₂ R ^c , –OS(=O) ₂ OR ^c , –S(=O)NR ^d R ^e , –OS(=O) ₂ NR ^d R ^e , and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O- C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl and C _6-11 aryl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl; R ³ is selected from the group consisting of H, C1-6 alkyl, CN, –C(=O)R ^f , –C(=O)OR ^g , – C(=O)NR ^h R ^j , –C(O)C(=O)R ^f , –NR ^h R ^j , –NR ^g C(=O)R ^f , –NR ^h C(=O)OR ^g , –NR ^h C(=O)NR ^h R ^j , – NR ^h S(=O)2R ^f , –NR ^h S(=O)2NR ^h R ^j , –OR ^g , –SR ^g , –OC(=O)R ^f , –OC(=O)NR ^h R ^j , –OC(=O)OR ^g , – S(=O)2R ^g , –S(=O)R ^g , –OS(=O)R ^g , –OS(=O)2R ^g , –OS(=O)2OR ^g , –S(=O)NR ^h R ^j , – OS(=O)2NR ^h R ^j , and –S(=O)2NR ^h R ^j , where said C1-6 alkyl is optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl and O-C1-6 alkyl; R ⁴ is selected from the group consisting of hydrogen, C1-10alkyl optionally substituted by one or more R ^a4 , C2-10alkenyl optionally substituted by one or more R ^a4 , C2-6alkynyl optionally substituted by one or more R ^a4 , C6-15aryl optionally substituted by one or more R ^a4 , C6-15aryl(C1-6)alkyl optionally substituted by one or more R ^a4 , C3-11cycloalkyl optionally substituted by one or more R ^a4 , C3-11cycloalkyl(C1-6)alkyl optionally substituted by one or more R ^a4 , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a4 , 4-15 membered heterocycloalkyl(C1-6)alkyl optionally substituted by one or more R ^a4 , 4-15 membered heteroaryl optionally substituted by one or more R ^a4 , and 4-15 membered heteroaryl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , CN, –C(=O)R ^f , –C(=O)OR ^g , – C(=O)NR ^h R ^j , –C(O)C(=O)R ^f , –OR ^g , –SR ^g , –OC(=O)R ^f , –OC(=O)NR ^h R ^j , –OC(=O)OR ^g , – S(=O) ₂ R ^g , –S(=O)R ^g , –OS(=O)R ^g , –OS(=O) ₂ R ^g , –OS(=O) ₂ OR ^g , –S(=O)NR ^h R ^j , – OS(=O) ₂ NR ^h R ^j , and –S(=O) ₂ NR ^h R ^j ; where each R ^a4 is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _{1- 6} haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , – NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O) ₂ R ^b , –NR ^d S(=O) ₂ NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , – OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O) ₂ R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O) ₂ R ^c , – OS(=O) ₂ OR ^c , –S(=O)NR ^d R ^e , –OS(=O) ₂ NR ^d R ^e , and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O- C _1-6 alkyl, C _3-6 cycloalkyl, and 3-7 membered heterocycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl; wherein each R ^b and R ^f are independently selected from hydrogen, hydroxyl, halogen, CN, C _1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, C _6-15 aryl, C _6-15 aryl(C _1-6 )alkyl, C _3-11 cycloalkyl(C _1-6 )alkyl, 4-15 membered heterocycloalkyl(C1-6)alkyl, and 4-15 membered heteroaryl(C1-6)alkyl, wherein said C1-6 alkyl, C6-15 aryl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C6- 15aryl(C1-6)alkyl, C3-11cycloalkyl(C1-6)alkyl, 4-15 membered heterocycloalkyl(C1-6)alkyl, and 4- 15 membered heteroaryl(C1-6)alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO2, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl; wherein each R ^c and R ^g are independently selected from hydrogen, hydroxyl, halogen, CN, C1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl and C6-15 aryl, wherein said C1-6 alkyl, C6-15 aryl, 3-7 membered heterocycloalkyl 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, nitro, amino, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl and O-C1-6 alkyl; wherein each R ^d and R ^h are independently selected from hydrogen, hydroxyl, halogen, CN, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkyl and O-C1-6 alkyl; wherein each R ^e and R ^j are independently selected from hydrogen, hydroxyl, halogen, CN, C _1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, C _6-15 aryl, C _6-15 aryl(C _1-6 )alkyl, C _3-11 cycloalkyl(C _1-6 )alkyl, 4-15 membered heterocycloalkyl(C _1-6 )alkyl, and 4-15 membered heteroaryl(C _1-6 )alkyl, wherein said C _1-6 alkyl, C _6-15 aryl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C _3-6 cycloalkyl, C _{6- 15} aryl(C _1-6 )alkyl, C _3-11 cycloalkyl(C _1-6 )alkyl, 4-15 membered heterocycloalkyl(C _1-6 )alkyl, and 4- 15 membered heteroaryl(C _1-6 )alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO ₂ , C _1-6 haloalkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl; or wherein R ^d and R ^e , when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more for heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more R ^k ; wherein R ^h and R ^j , when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more for heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more R ^k ; where R ^k is selected from hydrogen, =O, halogen, CN, NH ₂ , NH(C _1-6 alkyl), N(C _1-6 alkyl) ₂ , C _1-6 haloalkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl; and P ³ is a nitrogen protecting of formula -SO2R ⁶ wherein R ⁶ is selected from C1-6 alkyl, C1-6 haloalkyl, CH2CH2SiMe3, or a phenyl group optionally substituted with one or more groups selected from NO2, halogen and methyl. 112. A compound of formula II, or a salt thereof:

(II) wherein R ¹ is selected from the group consisting of hydrogen, C _1-10 alkyl optionally substituted by one or more R ^a1 , C _2-10 alkenyl optionally substituted by one or more R ^a1 , C _2-6 alkynyl optionally substituted by one or more R ^a1 , C _6-15 aryl optionally substituted by one or more R ^a1 , C6-15aryl(C1-6)alkyl optionally substituted by one or more R ^a1 , C3-11cycloalkyl optionally substituted by one or more R ^a1 , C3-11cycloalkyl(C1-6)alkyl optionally substituted by one or more R ^a1 , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a1 , 4-15 membered heterocycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a1 , 4-15 membered heteroaryl optionally substituted by one or more R ^a1 , and 4-15 membered heteroaryl(C _1-6 )alkyl optionally substituted by one or more R ^a1 , –C(=O)R ^b , –C(=O)OR ^c , – C(=O)NR ^d R ^e , and –C(O)C(=O)R ^b ; where each R ^a1 is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _{1- 6} haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , – NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O) ₂ R ^b , –NR ^d S(=O) ₂ NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , – OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O) ₂ R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O) ₂ R ^c , – OS(=O) ₂ OR ^c , –S(=O)NR ^d R ^e , –OS(=O) ₂ NR ^d R ^e , and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O- C1-6 alkyl, C3-6 cycloalkyl, and 3-7 membered heterocycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl and O-C1-6 alkyl; R ² is selected from the group consisting of hydrogen, C1-10alkyl optionally substituted by one or more R ^a2 , C2-10alkenyl optionally substituted by one or more R ^a2 , C2-6alkynyl optionally substituted by one or more R ^a2 , C _6-15 aryl optionally substituted by one or more R ^a2 , C6-15aryl(C1-6)alkyl optionally substituted by one or more R ^a2 , C3-11cycloalkyl optionally substituted by one or more R ^a2 , C3-11cycloalkyl(C1-6)alkyl optionally substituted by one or more R ^a2 , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a2 , 4-15 membered heterocycloalkyl(C1-6)alkyl optionally substituted by one or more R ^a2 , 4-15 membered heteroaryl optionally substituted by one or more R ^a2 , and 4-15 membered heteroaryl(C1-6)alkyl optionally substituted by one or more R ^a2 , –C(=O)R ^b , –C(=O)OR ^c , – C(=O)NR ^d R ^e , and –C(O)C(=O)R ^b ; where each R ^a2 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1- 6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , – NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O)2R ^b , –NR ^d S(=O)2NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , – OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O)2R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O)2R ^c , – OS(=O) ₂ OR ^c , –S(=O)NR ^d R ^e , –OS(=O) ₂ NR ^d R ^e , and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O- C _1-6 alkyl, C _3-6 cycloalkyl, and 3-7 membered heterocycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl; or R ¹ is absent and R ² combines with the nitrogen to which it is attached to form an imino group of formula =CR ^w R ^x , an amidine of formula =C(R ^w )(NR ^y R ^z ), or a guanidine of formula =C(NR ^y R ^z ) ₂ where R ^w , R ^x are independently C _1-6 alkyl and R ^y and R ^z are independently selected from hydrogen and C _1-6 alkyl; or R ¹ and R ² together with the nitrogen atom to which they are attached form a 3-15 membered heterocycloalkyl ring or 4-15 membered heteroaryl ring, each independently and optionally containing one or more further heteroatoms selected from O, N, and S and wherein each ring is independently and optionally substituted with one or more R ^a3 ; where each R ^a3 is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _{1- 6} haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-15 membered heterocycloalkyl, 4-15 membered heteroaryl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , –NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O) ₂ R ^b , –NR ^d S(=O) ₂ NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , –OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O) ₂ R ^c , –S(=O)R ^c , –OS(=O)R ^c , – OS(=O)2R ^c , –OS(=O)2OR ^c , –S(=O)NR ^d R ^e , –OS(=O)2NR ^d R ^e , and –S(=O)2NR ^d R ^e , where said C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, C6-11 aryl, 3-15 membered heterocycloalkyl, and 4-15 membered heteroaryl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl; R is selected from the group consisting of C1-10alkyl optionally substituted by one or more R ^a , C2-10alkenyl optionally substituted by one or more R ^a , C2-6alkynyl optionally substituted by one or more R ^a , C6-15aryl optionally substituted by one or more R ^a , C6-15aryl(C1- 6)alkyl optionally substituted by one or more R ^a , C3-11cycloalkyl optionally substituted by one or more R ^a , C3-11cycloalkyl(C1-6)alkyl optionally substituted by one or more R ^a , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a , 4-15 membered heterocycloalkyl(C1- 6)alkyl optionally substituted by one or more R ^a , 4-15 membered heteroaryl optionally substituted by one or more R ^a , and 4-15 membered heteroaryl(C1-6)alkyl optionally substituted by one or more R ^a ; where each R ^a is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, C6-11 aryl, – C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , – NR ^d C(=O)OR ^c , –NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O) ₂ R ^b , –NR ^d S(=O) ₂ NR ^d R ^e , –OR ^c , –SR ^c , – OC(=O)R ^b , –OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O) ₂ R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O) ₂ R ^c , –OS(=O) ₂ OR ^c , –S(=O)NR ^d R ^e , –OS(=O) ₂ NR ^d R ^e , and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O- C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl and C _6-11 aryl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl; wherein each R ^b is independently selected from hydrogen, hydroxyl, halogen, CN, C _1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, C _6-15 aryl, C _6-15 aryl(C _1-6 )alkyl, C _3-11 cycloalkyl(C _1-6 )alkyl, 4-15 membered heterocycloalkyl(C _1-6 )alkyl, and 4-15 membered heteroaryl(C _1-6 )alkyl, wherein said C _1-6 alkyl, C _6-15 aryl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C _3-6 cycloalkyl, C _{6- 15} aryl(C _1-6 )alkyl, C _3-11 cycloalkyl(C _1-6 )alkyl, 4-15 membered heterocycloalkyl(C _1-6 )alkyl, and 4- 15 membered heteroaryl(C _1-6 )alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO ₂ , C _1-6 haloalkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl; wherein each R ^c is independently selected from hydrogen, hydroxyl, halogen, CN, C1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl and C6-15 aryl, wherein said C1-6 alkyl, C6-15 aryl, 3-7 membered heterocycloalkyl 5- 6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, nitro, amino, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl and O-C1-6 alkyl; wherein each R ^d is independently selected from hydrogen, hydroxyl, halogen, CN, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkyl and O-C1-6 alkyl; wherein each R ^e is independently selected from hydrogen, hydroxyl, halogen, CN, C1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, C6-15 aryl, C6-15aryl(C1-6)alkyl, C3-11cycloalkyl(C1-6)alkyl, 4-15 membered heterocycloalkyl(C1-6)alkyl, and 4-15 membered heteroaryl(C1-6)alkyl, wherein said C1-6 alkyl, C6-15 aryl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C6- 15aryl(C1-6)alkyl, C3-11cycloalkyl(C1-6)alkyl, 4-15 membered heterocycloalkyl(C1-6)alkyl, and 4- 15 membered heteroaryl(C1-6)alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO ₂ , C _1-6 haloalkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl; or wherein R ^d and R ^e , when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more for heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more R ^k ; where R ^k is selected from hydrogen, =O, halogen, CN, NH ₂ , NH(C _1-6 alkyl), N(C _1-6 alkyl) ₂ , C _1-6 haloalkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl; P ² is a nitrogen protecting group selected from tert-octyl, tert-butyl and Si(R ⁵ ) ₃ wherein R ⁵ is selected from a C _1-4 alkyl group or a phenyl group; and P ³ is a nitrogen protecting of formula -SO ₂ R ⁶ wherein R ⁶ is selected from C _1-6 alkyl, C _{1- 6} haloalkyl, CH ₂ CH ₂ SiMe ₃ , or a phenyl group optionally substituted with one or more groups selected from NO _2, halogen and methyl. 113. A compound of formula III or a salt thereof: (III), wherein R is selected from the group consisting of C1-10alkyl optionally substituted by one or more R ^a , C2-10alkenyl optionally substituted by one or more R ^a , C2-6alkynyl optionally substituted by one or more R ^a , C6-15aryl optionally substituted by one or more R ^a , C6-15aryl(C1- 6)alkyl optionally substituted by one or more R ^a , C3-11cycloalkyl optionally substituted by one or more R ^a , C3-11cycloalkyl(C1-6)alkyl optionally substituted by one or more R ^a , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a , 4-15 membered heterocycloalkyl(C1- 6)alkyl optionally substituted by one or more R ^a , 4-15 membered heteroaryl optionally substituted by one or more R ^a , and 4-15 membered heteroaryl(C1-6)alkyl optionally substituted by one or more R ^a ; where each R ^a is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, C _6-11 aryl, – C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , – NR ^d C(=O)OR ^c , –NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O) ₂ R ^b , –NR ^d S(=O) ₂ NR ^d R ^e , –OR ^c , –SR ^c , – OC(=O)R ^b , –OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O) ₂ R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O) ₂ R ^c , –OS(=O) ₂ OR ^c , –S(=O)NR ^d R ^e , –OS(=O) ₂ NR ^d R ^e , and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O- C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl and C _6-11 aryl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl; wherein each R ^b is independently selected from hydrogen, hydroxyl, halogen, CN, C _1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, C _6-15 aryl, C _6-15 aryl(C _1-6 )alkyl, C _3-11 cycloalkyl(C _1-6 )alkyl, 4-15 membered heterocycloalkyl(C _1-6 )alkyl, and 4-15 membered heteroaryl(C _1-6 )alkyl, wherein said C _1-6 alkyl, C _6-15 aryl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C _3-6 cycloalkyl, C _{6- 15} aryl(C _1-6 )alkyl, C _3-11 cycloalkyl(C _1-6 )alkyl, 4-15 membered heterocycloalkyl(C _1-6 )alkyl, and 4- 15 membered heteroaryl(C _1-6 )alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO2, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl; wherein each R ^c is independently selected from hydrogen, hydroxyl, halogen, CN, C1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl and C6-15 aryl, wherein said C1-6 alkyl, C6-15 aryl, 3-7 membered heterocycloalkyl 5- 6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, nitro, amino, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl and O-C1-6 alkyl; wherein each R ^d is independently selected from hydrogen, hydroxyl, halogen, CN, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkyl and O-C1-6 alkyl; wherein each R ^e is independently selected from hydrogen, hydroxyl, halogen, CN, C1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, C6-15 aryl, C6-15aryl(C1-6)alkyl, C3-11cycloalkyl(C1-6)alkyl, 4-15 membered heterocycloalkyl(C1-6)alkyl, and 4-15 membered heteroaryl(C1-6)alkyl, wherein said C1-6 alkyl, C6-15 aryl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C6- 15aryl(C1-6)alkyl, C3-11cycloalkyl(C1-6)alkyl, 4-15 membered heterocycloalkyl(C1-6)alkyl, and 4- 15 membered heteroaryl(C1-6)alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO ₂ , C _1-6 haloalkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl; or wherein R ^d and R ^e , when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more for heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more R ^k ; where R ^k is selected from hydrogen, =O, halogen, CN, NH ₂ , NH(C _1-6 alkyl), N(C _1-6 alkyl) ₂ , C _1-6 haloalkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl; P ² is a nitrogen protecting group selected from tert-octyl, tert-butyl and Si(R ⁵ ) ₃ wherein R ⁵ is selected from a C _1-4 alkyl group or a phenyl group; P ³ is a nitrogen protecting of formula -SO ₂ R ⁶ wherein R ⁶ is selected from C _1-6 alkyl, C _{1- 6} haloalkyl, CH ₂ CH ₂ SiMe ₃ , or a phenyl group optionally substituted with one or more groups selected from NO _2, halogen and methyl; and X is a leaving group, preferably halo, more preferably F. 114. A compound of formula V, or a salt thereof: (V), wherein R is selected from the group consisting of C1-10alkyl optionally substituted by one or more R ^a , C2-10alkenyl optionally substituted by one or more R ^a , C2-6alkynyl optionally substituted by one or more R ^a , C6-15aryl optionally substituted by one or more R ^a , C6-15aryl(C1- 6)alkyl optionally substituted by one or more R ^a , C3-11cycloalkyl optionally substituted by one or more R ^a , C3-11cycloalkyl(C1-6)alkyl optionally substituted by one or more R ^a , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a , 4-15 membered heterocycloalkyl(C1- ₆ )alkyl optionally substituted by one or more R ^a , 4-15 membered heteroaryl optionally substituted by one or more R ^a , and 4-15 membered heteroaryl(C _1-6 )alkyl optionally substituted by one or more R ^a ; where each R ^a is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, C6-11 aryl, – C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , – NR ^d C(=O)OR ^c , –NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O) ₂ R ^b , –NR ^d S(=O) ₂ NR ^d R ^e , –OR ^c , –SR ^c , – OC(=O)R ^b , –OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O) ₂ R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O) ₂ R ^c , –OS(=O) ₂ OR ^c , –S(=O)NR ^d R ^e , –OS(=O) ₂ NR ^d R ^e , and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O- C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl and C _6-11 aryl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl; wherein each R ^b is independently selected from hydrogen, hydroxyl, halogen, CN, C _1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, C _6-15 aryl, C _6-15 aryl(C _1-6 )alkyl, C _3-11 cycloalkyl(C _1-6 )alkyl, 4-15 membered heterocycloalkyl(C _1-6 )alkyl, and 4-15 membered heteroaryl(C _1-6 )alkyl, wherein said C _1-6 alkyl, C6-15 aryl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C6- 15aryl(C1-6)alkyl, C3-11cycloalkyl(C1-6)alkyl, 4-15 membered heterocycloalkyl(C1-6)alkyl, and 4- 15 membered heteroaryl(C1-6)alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO2, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl; wherein each R ^c is independently selected from hydrogen, hydroxyl, halogen, CN, C1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl and C6-15 aryl, wherein said C1-6 alkyl, C6-15 aryl, 3-7 membered heterocycloalkyl 5- 6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, nitro, amino, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl and O-C1-6 alkyl; wherein each R ^d is independently selected from hydrogen, hydroxyl, halogen, CN, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkyl and O-C1-6 alkyl; wherein each R ^e is independently selected from hydrogen, hydroxyl, halogen, CN, C1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, C6-15 aryl, C6-15aryl(C1-6)alkyl, C3-11cycloalkyl(C1-6)alkyl, 4-15 membered heterocycloalkyl(C1-6)alkyl, and 4-15 membered heteroaryl(C1-6)alkyl, wherein said C1-6 alkyl, C6-15 aryl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C6- ₁₅ aryl(C _1-6 )alkyl, C _3-11 cycloalkyl(C _1-6 )alkyl, 4-15 membered heterocycloalkyl(C _1-6 )alkyl, and 4- 15 membered heteroaryl(C _1-6 )alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO ₂ , C _1-6 haloalkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl; or wherein R ^d and R ^e , when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more for heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more R ^k ; where R ^k is selected from hydrogen, =O, halogen, CN, NH ₂ , NH(C _1-6 alkyl), N(C _1-6 alkyl) ₂ , C _1-6 haloalkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl; P ² is a nitrogen protecting group selected from tert-octyl, tert-butyl and Si(R ⁵ ) ₃ wherein R ⁵ is selected from a C _1-4 alkyl group or a phenyl group; and P ³ is a nitrogen protecting of formula -SO ₂ R ⁶ wherein R ⁶ is selected from C _1-6 alkyl, C _{1- 6} haloalkyl, CH ₂ CH ₂ SiMe ₃ , or a phenyl group optionally substituted with one or more groups selected from NO _2, halogen and methyl. 115. A compound of formula VI, or a salt thereof: (VI), wherein R is selected from the group consisting of C1-10alkyl optionally substituted by one or more R ^a , C2-10alkenyl optionally substituted by one or more R ^a , C2-6alkynyl optionally substituted by one or more R ^a , C6-15aryl optionally substituted by one or more R ^a , C6-15aryl(C1- 6)alkyl optionally substituted by one or more R ^a , C3-11cycloalkyl optionally substituted by one or more R ^a , C3-11cycloalkyl(C1-6)alkyl optionally substituted by one or more R ^a , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a , 4-15 membered heterocycloalkyl(C1- 6)alkyl optionally substituted by one or more R ^a , 4-15 membered heteroaryl optionally substituted by one or more R ^a , and 4-15 membered heteroaryl(C1-6)alkyl optionally substituted by one or more R ^a ; where each R ^a is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, C _6-11 aryl, – C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , – NR ^d C(=O)OR ^c , –NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O) ₂ R ^b , –NR ^d S(=O) ₂ NR ^d R ^e , –OR ^c , –SR ^c , – OC(=O)R ^b , –OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O) ₂ R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O) ₂ R ^c , –OS(=O) ₂ OR ^c , –S(=O)NR ^d R ^e , –OS(=O) ₂ NR ^d R ^e , and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O- C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl and C _6-11 aryl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl; wherein each R ^b is independently selected from hydrogen, hydroxyl, halogen, CN, C _1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, C _6-15 aryl, C _6-15 aryl(C _1-6 )alkyl, C _3-11 cycloalkyl(C _1-6 )alkyl, 4-15 membered heterocycloalkyl(C _1-6 )alkyl, and 4-15 membered heteroaryl(C _1-6 )alkyl, wherein said C _1-6 alkyl, C _6-15 aryl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C _3-6 cycloalkyl, C _{6- 15} aryl(C _1-6 )alkyl, C _3-11 cycloalkyl(C _1-6 )alkyl, 4-15 membered heterocycloalkyl(C _1-6 )alkyl, and 4- 15 membered heteroaryl(C _1-6 )alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO2, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl; wherein each R ^c is independently selected from hydrogen, hydroxyl, halogen, CN, C1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl and C6-15 aryl, wherein said C1-6 alkyl, C6-15 aryl, 3-7 membered heterocycloalkyl 5- 6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, nitro, amino, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl and O-C1-6 alkyl; wherein each R ^d is independently selected from hydrogen, hydroxyl, halogen, CN, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkyl and O-C1-6 alkyl; wherein each R ^e is independently selected from hydrogen, hydroxyl, halogen, CN, C1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, C6-15 aryl, C6-15aryl(C1-6)alkyl, C3-11cycloalkyl(C1-6)alkyl, 4-15 membered heterocycloalkyl(C1-6)alkyl, and 4-15 membered heteroaryl(C1-6)alkyl, wherein said C1-6 alkyl, C6-15 aryl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C6- 15aryl(C1-6)alkyl, C3-11cycloalkyl(C1-6)alkyl, 4-15 membered heterocycloalkyl(C1-6)alkyl, and 4- 15 membered heteroaryl(C1-6)alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO ₂ , C _1-6 haloalkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl; or wherein R ^d and R ^e , when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more for heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more R ^k ; where R ^k is selected from hydrogen, =O, halogen, CN, NH ₂ , NH(C _1-6 alkyl), N(C _1-6 alkyl) ₂ , C _1-6 haloalkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl; and P ² is a nitrogen protecting group selected from tert-octyl, tert-butyl and Si(R ⁵ ) ₃ wherein R ⁵ is selected from a C _1-4 alkyl group or a phenyl group. 116. A compound or a process according to any one of the preceding paragraphs, wherein R is selected from the group consisting of C _1-10 alkyl optionally substituted by one or more R ^a , C _2-10 alkenyl optionally substituted by one or more R ^a , C _2-6 alkynyl optionally substituted by one or more R ^a , C _6-15 aryl optionally substituted by one or more R ^a , C _6-15 aryl(C _1-6 )alkyl optionally substituted by one or more R ^a , C3-11cycloalkyl optionally substituted by one or more R ^a , C3- 11cycloalkyl(C1-6)alkyl optionally substituted by one or more R ^a , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a , 4-15 membered heterocycloalkyl(C1- 6)alkyl optionally substituted by one or more R ^a , 4-15 membered heteroaryl optionally substituted by one or more R ^a , and 4-15 membered heteroaryl(C _1-6 )alkyl optionally substituted by one or more R ^a . 117. A compound or a process according to any one of the preceding paragraphs, wherein R is selected from the group consisting of C1-6alkyl optionally substituted by one or more R ^a , C6-12aryl optionally substituted by one or more R ^a , C3-7cycloalkyl optionally substituted by one or more R ^a , 5-12 membered heterocycloalkyl optionally substituted by one or more R ^a , and 5- 12 membered heteroaryl optionally substituted by one or more R ^a . 118. A compound or a process according to any one of the preceding paragraphs, wherein R is selected from the group consisting of C6-12aryl optionally substituted by one or more R ^a , 5-12 membered heterocycloalkyl optionally substituted by one or more R ^a , and 5-12 membered heteroaryl optionally substituted by one or more R ^a . 119. A compound or a process according to any one of the preceding paragraphs, wherein R is selected from the group consisting of phenyl optionally substituted by one or more R ^a , 5- 7 membered heterocycloalkyl optionally substituted by one or more R ^a , and 5-6 membered heteroaryl optionally substituted by one or more R ^a . 120. A compound or a process according to any one of the preceding paragraphs, wherein R ^a is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, –C(=O)R ^b , – C(=O)NR ^d R ^e , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d S(=O) ₂ R ^b , –OR ^c , –SR ^c , –OC(=O)R ^b , –S(=O) ₂ R ^c , – S(=O)R ^c , –OS(=O)R ^c , –OS(=O) ₂ R ^c , –OS(=O) ₂ OR ^c , –S(=O)NR ^d R ^e , –OS(=O) ₂ NR ^d R ^e , and – S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. 121. A compound or a process according to any one of the preceding paragraphs, wherein R ^a is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, where said C _1-6 alkyl and O-C _1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. 122. A compound or a process according to any one of the preceding paragraphs, wherein R is selected from the group consisting of phenyl optionally substituted by one or more R ^a , 5- 7 membered heterocycloalkyl optionally substituted by one or more R ^a , and 5-6 membered heteroaryl optionally substituted by one or more R ^a , wherein R ^a is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, where said C1-6 alkyl and O-C1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. 123. A compound or a process according to any one of the preceding paragraphs, wherein R ¹ is selected from the group consisting of hydrogen, C1-10alkyl optionally substituted by one or more R ^a1 , C2-10alkenyl optionally substituted by one or more R ^a1 , C2-6alkynyl optionally substituted by one or more R ^a1 , C6-15aryl optionally substituted by one or more R ^a1 , C6-15aryl(C1- 6)alkyl optionally substituted by one or more R ^a1 , C3-11cycloalkyl optionally substituted by one or more R ^a1 , C3-11cycloalkyl(C1-6)alkyl optionally substituted by one or more R ^a1 , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a1 , 4-15 membered heterocycloalkyl(C1-6)alkyl optionally substituted by one or more R ^a1 , 4-15 membered heteroaryl optionally substituted by one or more R ^a1 , and 4-15 membered heteroaryl(C1-6)alkyl optionally substituted by one or more R ^a1 , –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , and – C(O)C(=O)R ^b . 124. A compound or a process according to any one of the preceding paragraphs, wherein R ¹ is selected from the group consisting of hydrogen, C1-6alkyl optionally substituted by one or more R ^a1 , C _2-6 alkenyl optionally substituted by one or more R ^a1 , C _2-6 alkynyl optionally substituted by one or more R ^a1 , –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , and –C(O)C(=O)R ^b . 125. A compound or a process according to any one of the preceding paragraphs, wherein R ¹ is selected from the group consisting of hydrogen, C _1-6 alkyl optionally substituted by one or more R ^a1 , –C(=O)R ^b , and –C(=O)NR ^d R ^e . 126. A compound or a process according to any one of the preceding paragraphs, wherein R ¹ is hydrogen or C _1-6 alkyl optionally substituted by one or more R ^a1 . 127. A compound or a process according to any one of the preceding paragraphs, wherein R ^a1 is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, –C(=O)R ^b , – C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , – NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O)2R ^b , –NR ^d S(=O)2NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , – OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O)2R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O)2R ^c , – OS(=O)2OR ^c , –S(=O)NR ^d R ^e , –OS(=O)2NR ^d R ^e , and –S(=O)2NR ^d R ^e , where said C1-6 alkyl, O- C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. 128. A compound or a process according to any one of the preceding paragraphs, wherein R ^a1 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, –NR ^d R ^e , –OR ^c , –SR ^c , where said C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. 129. A compound or a process according to any one of the preceding paragraphs, wherein R ^a1 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, where said C _1-6 alkyl and O-C _1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. 130. A compound or a process according to any one of the preceding paragraphs, wherein R ^a1 is independently selected from hydroxyl, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, where said C _1-6 alkyl and O-C _1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. 131. A compound or a process according to any one of the preceding paragraphs, wherein R ² is selected from the group consisting of hydrogen, C _1-6 alkyl optionally substituted by one or more R ^a2 , C _2-6 alkenyl optionally substituted by one or more R ^a2 , C _2-6 alkynyl optionally substituted by one or more R ^a2 , C _6-12 aryl optionally substituted by one or more R ^a2 , C _6-12 aryl(C _{1- 3} )alkyl optionally substituted by one or more R ^a2 , C _3-7 cycloalkyl optionally substituted by one or more R ^a2 , C _3-7 cycloalkyl(C _1-3 )alkyl optionally substituted by one or more R ^a2 , 3-12 membered heterocycloalkyl optionally substituted by one or more R ^a2 , 4-12 membered heterocycloalkyl(C _1-3 )alkyl optionally substituted by one or more R ^a2 , 4-12 membered heteroaryl optionally substituted by one or more R ^a2 , and 4-12 membered heteroaryl(C _1-3 )alkyl optionally substituted by one or more R ^a2 , –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , and – C(O)C(=O)R ^b . 132. A compound or a process according to any one of the preceding paragraphs, wherein R ² is selected from the group consisting of hydrogen, C1-6alkyl optionally substituted by one or more R ^a2 , C _2-6 alkenyl optionally substituted by one or more R ^a2 , C _2-6 alkynyl optionally substituted by one or more R ^a2 , C _6-11 aryl optionally substituted by one or more R ^a2 , C _3- 7cycloalkyl optionally substituted by one or more R ^a2 , 5-12 membered heterocycloalkyl optionally substituted by one or more R ^a2 , 5-12 membered heteroaryl optionally substituted by one or more R ^a2 , –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , and –C(O)C(=O)R ^b . 133. A compound or a process according to any one of the preceding paragraphs, wherein R ² is selected from the group consisting of hydrogen, C1-6alkyl optionally substituted by one or more R ^a2 , C2-6alkenyl optionally substituted by one or more R ^a2 , phenyl optionally substituted by one or more R ^a2 , C3-7cycloalkyl optionally substituted by one or more R ^a2 , 4-7 membered heterocycloalkyl optionally substituted by one or more R ^a2 , 5-6 membered heteroaryl optionally substituted by one or more R ^a2 , –C(=O)R ^b , and –C(=O)NR ^d R ^e . 134. A compound or a process according to any one of the preceding paragraphs, wherein R ² is hydrogen or C _1-6 alkyl optionally substituted by one or more R ^a2 . 135. A compound or a process according to any one of the preceding paragraphs, wherein R ^a2 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, –C(=O)R ^b , – C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d C(=O)OR ^c , – NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O) ₂ R ^b , –NR ^d S(=O) ₂ NR ^d R ^e , –OR ^c , –SR ^c , –OC(=O)R ^b , – OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O) ₂ R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O) ₂ R ^c , – OS(=O) ₂ OR ^c , –S(=O)NR ^d R ^e , –OS(=O) ₂ NR ^d R ^e , and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O- C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. 136. A compound or a process according to any one of the preceding paragraphs, wherein R ^a2 is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, –C(=O)R ^b , – C(=O)NR ^d R ^e , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d S(=O) ₂ R ^b , –OR ^c , –SR ^c , –OC(=O)R ^b , –S(=O) ₂ R ^c , – S(=O)R ^c , –OS(=O)R ^c , –S(=O)NR ^d R ^e and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O-C _1-6 alkyl, C _{3- 6} cycloalkyl, 3-7 membered heterocycloalkyl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. 137. A compound or a process according to any one of the preceding paragraphs, wherein R ^a2 is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, where said C1- 6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. 138. A compound or a process according to any one of the preceding paragraphs, wherein R ^a2 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, where said C1-6 alkyl and O-C1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. 139. A compound or a process according to any one of the preceding paragraphs, wherein R ^a2 is independently selected from hydroxyl, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, where said C1-6 alkyl and O-C1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. 140. A compound or a process according to any one of the preceding paragraphs, wherein R ¹ is absent and R ² combines with the nitrogen to which it is attached to form an imino group of formula =CR ^w R ^x , an amidine of formula =C(R ^w )(NR ^y R ^z ), or a guanidine of formula =C(NR ^y R ^z ) ₂ , where R ^w , R ^x are independently C _1-6 alkyl and R ^y and R ^z are independently selected from hydrogen and C _1-6 alkyl. 141. A compound or a process according to any one of the preceding paragraphs, wherein R ¹ and R ² together with the nitrogen atom to which they are attached form a 3-12 membered heterocycloalkyl ring or 4-12 membered heteroaryl ring, each independently and optionally containing one or more further heteroatoms selected from O, N, and S and wherein each ring is independently and optionally substituted with one or more R ^a3 . 142. A compound or a process according to any one of the preceding paragraphs, wherein R ¹ and R ² together with the nitrogen atom to which they are attached form a 5-7 membered heterocycloalkyl ring or 5-12 membered heteroaryl ring, each independently and optionally containing one or more further heteroatoms selected from O, N, and S and wherein each ring is independently and optionally substituted with one or more R ^a3 . 143. A compound or a process according to any one of the preceding paragraphs, wherein R ¹ and R ² together with the nitrogen atom to which they are attached form a 5-7 membered heterocycloalkyl ring or 5-6 membered heteroaryl ring, each independently and optionally containing one or more further heteroatoms selected from O, N, and S and wherein each ring is independently and optionally substituted with one or more R ^a3 . 144. A compound or a process according to any one of the preceding paragraphs, wherein R ^a3 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , – NR ^d C(=O)OR ^c , –NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O)2R ^b , –NR ^d S(=O)2NR ^d R ^e , –OR ^c , –SR ^c , – OC(=O)R ^b , –OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O)2R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O)2R ^c , –OS(=O)2OR ^c , –S(=O)NR ^d R ^e , –OS(=O)2NR ^d R ^e , and –S(=O)2NR ^d R ^e , where said C1-6 alkyl, O- C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. 145. A compound or a process according to any one of the preceding paragraphs, wherein R ^a3 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, –C(=O)R ^b , –C(=O)NR ^d R ^e , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d S(=O) ₂ R ^b , –OR ^c , –SR ^c , – OC(=O)R ^b , –S(=O) ₂ R ^c , –S(=O)R ^c , –OS(=O)R ^c , –S(=O)NR ^d R ^e and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. 146. A compound or a process according to any one of the preceding paragraphs, wherein R ^a3 is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl, where said C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. 147. A compound or a process according to any one of the preceding paragraphs, wherein R ^a3 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, where said C1-6 alkyl and O-C1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. 148. A compound or a process according to any one of the preceding paragraphs, wherein R ^a3 is independently selected from hydroxyl, =O, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O- C1-6 alkyl, where said C1-6 alkyl and O-C1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. 149. A compound or a process according to any one of the preceding paragraphs, wherein R ¹ and R ² together with the nitrogen atom to which they are attached form a 5-7 membered heterocycloalkyl ring or 5-6 membered heteroaryl ring, each independently and optionally containing one or more further heteroatoms selected from O, N, and S and wherein each ring is independently and optionally substituted with one or more substitutents selected from hydroxyl, =O, C1-6 haloalkyl, C1-6 alkyl, O-C1-6 alkyl, where said C1-6 alkyl is optionally substituted with one or more groups selected from hydroxyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. 150. A compound or a process according to any one of the preceding paragraphs, wherein R ¹ and R ² are independently selected from hydrogen or C _1-3 alkyl optionally substituted by one or more R ^a1 or R ^a2 respectively; or, R ¹ and R ² together with the nitrogen atom to which they are attached, form a 5-7 membered heterocycloalkyl ring or 5-6 membered heteroaryl ring, each independently and optionally containing one or more further heteroatoms selected from O, N, and S and wherein each ring is independently and optionally substituted with one or more R ^a3 . 151. A compound or a process according to any one of the preceding paragraphs, wherein R ³ is selected from the group consisting of H, C _1-6 alkyl, CN, –C(=O)R ^f , –C(=O)NR ^h R ^j , –OR ^g , –SR ^g , –OC(=O)R ^f , –OC(=O)NR ^h R ^j , –OC(=O)OR ^g , –S(=O) ₂ R ^g , –S(=O)R ^g , –OS(=O)R ^g , – OS(=O) ₂ R ^g , –OS(=O) ₂ OR ^g , –S(=O)NR ^h R ^j , –OS(=O) ₂ NR ^h R ^j , and –S(=O) ₂ NR ^h R ^j , where said C _1- 6 alkyl is optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl and O-C1-6 alkyl. 152. A compound or a process according to any one of the preceding paragraphs, wherein R ³ is selected from the group consisting of H, C _1-6 alkyl, CN, –C(=O)R ^f , –C(=O)OR ^g , – C(=O)NR ^h R ^j , –S(=O)2R ^g , –S(=O)R ^g , ––S(=O)NR ^h R ^j , and –S(=O)2NR ^h R ^j , where said C1-6 alkyl is optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1- 6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl and O-C1-6 alkyl. 153. A compound or a process according to any one of the preceding paragraphs, wherein R ³ is selected from the group consisting of H, C1-3 alkyl, CN, –C(=O)R ^f and –C(=O)NR ^h R ^j , where said C1-3 alkyl is optionally substituted with one or more groups selected from hydroxyl, CN, C1-3 haloalkyl, C1-3 haloalkoxy, C3-6 cycloalkyl, and O-C1-3 alkyl. 154. A compound or a process according to any one of the preceding paragraphs, wherein R ⁴ is selected from the group consisting of hydrogen, C1-10alkyl optionally substituted by one or more R ^a4 , C2-10alkenyl optionally substituted by one or more R ^a4 , C2-6alkynyl optionally substituted by one or more R ^a4 , C _6-15 aryl optionally substituted by one or more R ^a4 , C _6-15 aryl(C _{1- 6} )alkyl optionally substituted by one or more R ^a4 , C _3-11 cycloalkyl optionally substituted by one or more R ^a4 , C _3-11 cycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , 3-15 membered heterocycloalkyl optionally substituted by one or more R ^a4 , 4-15 membered heterocycloalkyl(C1-6)alkyl optionally substituted by one or more R ^a4 , 4-15 membered heteroaryl optionally substituted by one or more R ^a4 , and 4-15 membered heteroaryl(C1-6)alkyl optionally substituted by one or more R ^a4 , CN, –C(=O)R ^f , –C(=O)OR ^g , –C(=O)NR ^h R ^j , – C(O)C(=O)R ^f , –OR ^g , –SR ^g , –S(=O) ₂ R ^g , –S(=O)R ^g , –OS(=O)R ^g , –OS(=O) ₂ R ^g , –OS(=O) ₂ OR ^g , –S(=O)NR ^h R ^j , –OS(=O) ₂ NR ^h R ^j , and –S(=O) ₂ NR ^h R ^j . 155. A compound or a process according to any one of the preceding paragraphs, wherein R ⁴ is selected from the group consisting of hydrogen, C _1-10 alkyl optionally substituted by one or more R ^a4 , C _2-10 alkenyl optionally substituted by one or more R ^a4 , C _2-6 alkynyl optionally substituted by one or more R ^a4 , C _6-12 aryl optionally substituted by one or more R ^a4 , C _6-12 aryl(C _{1- 3} )alkyl optionally substituted by one or more R ^a4 , C _3-7 cycloalkyl optionally substituted by one or more R ^a4 , C _3-7 cycloalkyl(C _1-3 )alkyl optionally substituted by one or more R ^a4 , 3-12 membered heterocycloalkyl optionally substituted by one or more R ^a4 , 4-12 membered heterocycloalkyl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , 4-12 membered heteroaryl optionally substituted by one or more R ^a4 , and 4-12 membered heteroaryl(C _1-6 )alkyl optionally substituted by one or more R ^a4 , CN, –C(=O)R ^f , –C(=O)OR ^g , –C(=O)NR ^h R ^j , – C(O)C(=O)R ^f , –OR ^g , –SR ^g , –S(=O) ₂ R ^g , –S(=O)R ^g , –S(=O)NR ^h R ^j , and –S(=O) ₂ NR ^h R ^j . 156. A compound or a process according to any one of the preceding paragraphs, wherein R ⁴ is selected from the group consisting of hydrogen, C1-6alkyl optionally substituted by one or more R ^a4 , C2-6alkenyl optionally substituted by one or more R ^a4 , C2-6alkynyl optionally substituted by one or more R ^a4 , phenyl optionally substituted by one or more R ^a4 , phenyl(C1- 3)alkyl optionally substituted by one or more R ^a4 , 5-10 membered heteroaryl optionally substituted by one or more R ^a4 , and 5-10 membered heteroaryl(C1-6)alkyl optionally substituted by one or more R ^a4 , CN, –C(=O)R ^f , –C(=O)OR ^g , –C(=O)NR ^h R ^j , –OR ^g , and –SR ^g . 157. A compound or a process according to any one of the preceding paragraphs, wherein R ⁴ is selected from the group consisting of hydrogen, C1-6alkyl optionally substituted by one or more R ^a4 , C2-6alkynyl optionally substituted by one or more R ^a4 , phenyl optionally substituted by one or more R ^a4, , benzyl optionally substituted by one or more R ^a4, , –C(=O)R ^f , –C(=O)OR ^g , –C(=O)NR ^h R ^j and –SR ^g . 158. A compound or a process according to any one of the preceding paragraphs, wherein R ^a4 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, –C(=O)R ^b , –C(=O)OR ^c , –C(=O)NR ^d R ^e , –C(O)C(=O)R ^b , –NR ^d R ^e , –NR ^d C(=O)R ^b , – NR ^d C(=O)OR ^c , –NR ^d C(=O)NR ^d R ^e , –NR ^d S(=O) ₂ R ^b , –NR ^d S(=O) ₂ NR ^d R ^e , –OR ^c , –SR ^c , – OC(=O)R ^b , –OC(=O)NR ^d R ^e , –OC(=O)OR ^c , –S(=O)2R ^c , –S(=O)R ^c , –OS(=O)R ^c , –OS(=O)2R ^c , –OS(=O)2OR ^c , –S(=O)NR ^d R ^e , –OS(=O)2NR ^d R ^e , and –S(=O)2NR ^d R ^e , where said C1-6 alkyl, O- C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. 159. A compound or a process according to any one of the preceding paragraphs, wherein R ^a4 is independently selected from hydroxyl, =O, halogen, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, –C(=O)R ^b , –C(=O)NR ^d R ^e , –NR ^d R ^e , –NR ^d C(=O)R ^b , –NR ^d S(=O) ₂ R ^b , –OR ^c , –SR ^c , – OC(=O)R ^b , –S(=O) ₂ R ^c , –S(=O)R ^c , –OS(=O)R ^c , –S(=O)NR ^d R ^e and –S(=O) ₂ NR ^d R ^e , where said C _1-6 alkyl, O-C _1-6 alkyl, C _3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C _1-6 haloalkyl, C _1-6 haloalkoxy, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. 160. A compound or a process according to any one of the preceding paragraphs, wherein R ^a4 is independently selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, where said C1-6 alkyl and O-C1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. 161. A compound or a process according to any one of the preceding paragraphs, wherein R ^a4 is independently selected from hydroxyl, =O, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O- C1-6 alkyl, where said C1-6 alkyl and O-C1-6 alkyl are optionally substituted with one or more groups selected from hydroxyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. 162. A compound or a process according to any one of the preceding paragraphs, wherein R ^b and R ^f are independently selected from hydrogen, CN, 3-7 membered heterocycloalkyl, 5- 15 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, C6-15 aryl, C6-15aryl(C1-6)alkyl, C3-11cycloalkyl(C1-6)alkyl, 4-15 membered heterocycloalkyl(C1-6)alkyl, and 4-15 membered heteroaryl(C1-6)alkyl, wherein said C1-6 alkyl, C6-15 aryl, 3-7 membered heterocycloalkyl, 5-15 membered heteroaryl, C _3-6 cycloalkyl, C _6-15 aryl(C _1-6 )alkyl, C _3-11 cycloalkyl(C _1-6 )alkyl, 4-15 membered heterocycloalkyl(C _1-6 )alkyl, and 4-15 membered heteroaryl(C _1-6 )alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO ₂ , C _1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. 163. A compound or a process according to any one of the preceding paragraphs, wherein R ^b and R ^f are independently selected from hydrogen, 3-7 membered heterocycloalkyl, 5-12 membered heteroaryl, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, C _6-12 aryl, C _6-12 aryl(C _1-3 )alkyl, C _{3- 11} cycloalkyl(C _1-3 )alkyl, 4-12 membered heterocycloalkyl(C _1-3 )alkyl, and 4-12 membered heteroaryl(C _1-3 )alkyl, wherein said C _1-6 alkyl, C _6-12 aryl, 3-7 membered heterocycloalkyl, 5-12 membered heteroaryl, C _3-6 cycloalkyl, C _6-12 aryl(C _1-3 )alkyl, C _3-11 cycloalkyl(C _1-3 )alkyl, 4-12 membered heterocycloalkyl(C _1-3 )alkyl, and 4-12 membered heteroaryl(C _1-3 )alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO ₂ , C _1-6 haloalkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. 164. A compound or a process according to any one of the preceding paragraphs, wherein R ^b and R ^f are independently selected from hydrogen, phenyl, phenyl(C _1-3 )alkyl, wherein said phenyl and phenyl(C1-3)alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO2, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. 165. A compound or a process according to any one of the preceding paragraphs, wherein each R ^c and R ^g are independently selected from hydrogen, halogen, CN, C _1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl and C6-15 aryl, wherein said C1-6 alkyl, C6-15 aryl, 3-7 membered heterocycloalkyl 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, nitro, amino, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl and O-C1-6 alkyl. 166. A compound or a process according to any one of the preceding paragraphs, wherein each R ^c and R ^g are independently selected from hydrogen, C1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C1-6 alkyl and phenyl, wherein said C1-6 alkyl, C6-15 aryl, 3-7 membered heterocycloalkyl, and 5-6 membered heteroaryl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, nitro, amino, C1-6 haloalkyl, C3- 6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl and O-C1-6 alkyl. 167. A compound or a process according to any one of the preceding paragraphs, wherein R ^d and R ^h are independently selected from hydrogen, CN, C _1-6 haloalkyl, C _3-6 cycloalkyl, and C _1-6 alkyl. 168. A compound or a process according to any one of the preceding paragraphs, wherein R ^d and R ^h are independently selected from hydrogen, and C _1-3 alkyl. 169. A compound or a process according to any one of the preceding paragraphs, wherein R ^e and R ^j are independently selected from hydrogen, CN, C _1-6 haloalkyl, 3-7 membered heterocycloalkyl, 5-15 membered heteroaryl, C _3-6 cycloalkyl, C _1-6 alkyl, O-C _1-6 alkyl, C _6-15 aryl, C _6-15 aryl(C _1-6 )alkyl, C _3-11 cycloalkyl(C _1-6 )alkyl, 4-15 membered heterocycloalkyl(C _1-6 )alkyl, and 4-15 membered heteroaryl(C _1-6 )alkyl, wherein said C _1-6 alkyl, C _6-15 aryl, 3-7 membered heterocycloalkyl, 5-15 membered heteroaryl, C _3-6 cycloalkyl, C _6-15 aryl(C _1-6 )alkyl, C _{3- 11} cycloalkyl(C _1-6 )alkyl, 4-15 membered heterocycloalkyl(C _1-6 )alkyl, and 4-15 membered heteroaryl(C _1-6 )alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO ₂ , C _1-6 haloalkyl, C _3-6 cycloalkyl, C _6-11 aryl, 3-7 membered heterocycloalkyl, C _{1- 6} alkyl, O-C _1-6 alkyl, NH ₂ , NHR’, and NR’R’’, where R’ and R’’ are independently selected from C _1-4 alkyl. 170. A compound or a process according to any one of the preceding paragraphs, wherein R ^e and R ^j are independently selected from hydrogen, C _3-6 cycloalkyl, C _1-6 alkyl, C _6-12 aryl, C _6- 12aryl(C1-3)alkyl, C3-11cycloalkyl(C1-3)alkyl, wherein said C1-6 alkyl, C6-12 aryl, C3-6 cycloalkyl, C6- 12aryl(C1-3)alkyl, and C3-11cycloalkyl(C1-3)alkyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO2, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. 171. A compound or a process according to any one of the preceding paragraphs, wherein R ^e and R ^j are independently selected from hydrogen, C1-3 alkyl, phenyl, and pheny(C1-3)alkyl, wherein said C1-3 alkyl, phenyl and phenyl(C1-3)alkyl, , are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NO2, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11 aryl, 3-7 membered heterocycloalkyl, C1-6 alkyl, O-C1-6 alkyl, NH2, NHR’, and NR’R’’, where R’ and R’’ are independently selected from C1-4 alkyl. 172. A compound or a process according to any one of the preceding paragraphs, wherein R ^d and R ^e , when attached to the same atom, together with the atom to which they are attached form a 5-7 membered ring, optionally containing one or more for heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more R ^k . 173. A compound or a process according to any one of the preceding paragraphs, wherein R ^h and R ^j , when attached to the same atom, together with the atom to which they are attached form a 5-7 membered ring, optionally containing one or more for heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more R ^k . 174. A compound or a process according to any one of the preceding paragraphs, wherein R ^k is selected from =O, halogen, CN, NH ₂ , NH(C _1-6 alkyl), N(C _1-6 alkyl) ₂ , C _1-6 haloalkyl, C _3-6 cycloalkyl, phenyl, 5-7 membered heterocycloalkyl, C _1-6 alkyl and O-C _1-6 alkyl. 175. A compound or a process according to any one of the preceding paragraphs, wherein R ^k is selected from =O, halogen, CN, NH ₂ , NH(C _1-3 alkyl), N(C ₁₃ alkyl) ₂ , C _1-6 haloalkyl, C _1-6 alkyl and O-C _1-6 alkyl. 176. A compound or a process according to any one of the preceding paragraphs, wherein R’ and R’’ are independently selected from methyl, ethyl or propyl; preferably methyl or ethyl. 177. A compound or a process according to any one of the preceding paragraphs, wherein (i) when R is methyl, ethyl or butyl then R ³ and R ⁴ cannot both be methyl; and (ii) when R is optionally substituted phenyl then R ³ and R ⁴ cannot both be -SO ₂ CF ₃ . [00335] Though the present invention may relate to any compound or particular group of compounds defined herein by way of optional, preferred or suitable features or otherwise in terms of particular embodiments, the present invention may also relate to any compound or particular group of compounds that specifically excludes said optional, preferred or suitable features or particular embodiments. EXAMPLES [00336] The following examples are provided solely to illustrate the present invention and are not intended to limit the scope of the invention, as described herein. [00337] The compounds of the invention may be prepared using synthetic techniques that are known in the art (as illustrated by the examples herein). [00338] Several methods for the chemical synthesis of the compounds of the present application are described herein. These and/or other well-known methods may be modified and/or adapted in various ways in order to facilitate the synthesis of additional compounds within the scope of the present application and claims. Such alternative methods and modifications should be understood as being within the spirit and scope of this application and claims. Accordingly, it should be understood that the methods set forth in the following descriptions, schemes and examples are intended for illustrative purposes and are not to be construed as limiting the scope of the disclosure. General Considerations [00339] Handling techniques: Reactions were performed under inert nitrogen atmosphere with anhydrous solvent unless otherwise stated. All glassware was oven dried at >100 °C and allowed to cool to room temperature under positive pressure of nitrogen. Reactions were monitored by TLC until deemed complete using aluminum backed silica plates. Plates were visualised under ultraviolet light (254 nm) and/or by staining with KMnO ₄ solution. Cooling of reaction mixtures to 0 °C was achieved using an ice-water bath. Cooling of reaction mixtures to -78 °C was achieved using a dry ice-acetone bath. ‘Room temperature’ refers to an ambient temperature of 21 ± 2 °C. [00340] Reagents: Reagents were purchased from Sigma-Aldrich Chemical Co. Ltd., Alfa Aesar, Tokyo Chemical Industry UK or Fluorochem Ltd. and were used as supplied. N- Sulfinyl-tert-octylamine which was prepared by literature method. Anhydrous solvents were purified by filtration through dried alumina columns using the University of Oxford internal solvent drying system (Innovative Technology Inc. PS-400-7) and sparged with nitrogen before use. All inert gases were sourced from the University of Oxford internal supplies and dried through CaCl ₂ drying columns. Grignard and organolithium reagents were titrated against salicylaldehyde phenylhydrazone ¹⁰ . Flash column chromatography was carried out using matrix 60 silica gel. ‘Petrol’ refers to the fraction of light petroleum ether boiling in the range 40-60 °C. [00341] NMR Spectroscopy: ¹ H-NMR spectra were obtained on a Bruker AVIII400 (400 MHz) spectrometer using the residual solvent as an internal standard. ¹³ C-NMR spectra were obtained on a Bruker AVIII400 (101 MHz) using the residual solvent as an internal standard. ¹⁹ F-NMR spectra were obtained on a Bruker AVIII400 (377 MHz) spectrometer. All reported ¹ H and ¹³ C chemical shifts (δH, δC) are referenced to the residual signal of deuterated solvents (CDCl3: δH = 7.26 ppm, δC = 77.16 ppm; (CD3)2SO: δH = 2.50 ppm, δC = 39.52 ppm; (CD3)2CO: δH = 2.05 ppm, δC = 206.26 ppm). ¹⁹ F chemical shifts (δF) are referenced externally to CFCl3 (δF = 0.0 ppm). Chemical shifts (δ) are reported in parts per million (ppm) to the nearest 0.01 ppm for ¹ H NMR, and 0.1 ppm for ¹³ C and ¹⁹ F NMR. Coupling constants (J) are reported in Hertz (Hz). Multiplicities are reported as followings: s (singlet), d (doublet), t (triplet), q (quartet), pent. (pentet), m (multiplet), br. (broad signal), app. (apparent). [00342] Mass Spectroscopy: Low resolution ESI mass spectra were recorded on a Waters LCT Premier spectrometer. High resolution mass spectrometry measurements were recorded on a Bruker Daltronics MicroTOF (ESI) spectrometer or on a Micromass LCT (FI) spectrometer by the internal service at Chemistry Research Laboratory, University of Oxford. Samples for mass spectra were prepared as 1 mg/mL solution in MeOH (LRMS, HRMS-ESI) or submitted neat (HRMS-FI). [00343] IR Spectroscopy: Infrared spectra were recorded as thin films on a Bruker Tensor 27 FT-IR spectrometer. [00344] Melting point: Melting points were determined using a Stuart Scientific Melting Point Apparatus SMP1. [00345] Optical rotation: Optical rotations were measured on a Schmidt Haensch UniPol L2000 polarimeter at 589 nm, 25 °C. is expressed in deg cm ³ g ^-1 dm ^-1 and c is 3 expressed in g/100 cm . Synthesis and Characterisation [00346] General Procedure A - Sulfinamidine Synthesis [00347] N-Sulfinyl-tert-octylamine P1 (1.00 equiv.) was dissolved in anhydrous THF (0.5 M) in an oven-dried round-bottom flask. The mixture was cooled to -30 °C before LiHMDS (1.0 M in THF, 1.00 equiv.) was added. The reaction was stirred at - 30 °C for 5 min and then warmed to 0 °C and stirred for another 10 min. TMSCl (1.00 equiv.) was added and the reaction was stirred at 0 °C for 10 min. The organometallic reagent (1.20 equiv.) was then added and the reaction was stirred at 0 °C for 10 min. The reaction mixture was then quenched with sat. aq. tetrasodium EDTA solution. Ethyl acetate was added and the organic layers was separated. The aqueous layers was further extracted with ethyl acetate ×2. The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude mixture was dissolved in anhydrous CH2Cl2 (0.2 M) in an oven-dried round-bottom flask before Et3N (1.20 equiv.) and NsCl (1.10 equiv.) were added. The reaction was stirred at room temperature for 12 h until completion (judged by TLC). The reaction was quenched with water and extracted with CH2Cl2 ×3. The combined organic layers were dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure and purified by flash column chromatography to afford the sulfinamidine product. [00348] N-(S-(4-Fluorophenyl)-N-(2,4,4-trimethylpentan-2-yl)sulfinim idoyl)-4- nitrobenzenesulfonamide (P2) N-Sulfinyl-tert-octylamine P1 (2.75 g, 15.68 mmol, 1.00 equiv.) was dissolved in anhydrous THF (31.4 mL) in an oven-dried 250 mL round-bottom flask. The mixture was cooled to -30 °C before LiHMDS (15.68 mL, 1.0 M in THF, 15.68 mmol, 1.00 equiv.) was added. The reaction was stirred at - 30 °C for 5 min and then warmed to 0 °C and stirred for another 10 min. TMSCl (1.99 mL, 15.68 mmol, 1.00 equiv.) was added and the reaction was stirred at 0 °C for 10 min. 4-Fluorophenylmagnesium bromide solution (19.20 mL, 0.98 M in THF, 18.82 mmol, 1.20 equiv.) was then added and the reaction was stirred at 0 °C for 10 min. The reaction mixture was then quenched with sat. aq. tetrasodium EDTA solution (200 mL). Ethyl acetate (150 mL) was added and the organic layers was separated. The aqueous layers was further extracted with ethyl acetate (2 × 80 mL). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The crude mixture was dissolved in anhydrous CH2Cl2 (78.0 mL) in an oven-dried 250 mL round-bottom flask before Et3N (2.62 mL, 18.82 mmol, 1.20 equiv.) and NsCl (3.82 g, 17.25 mmol, 1.10 equiv.) were added. The reaction was stirred at room temperature for 12 h until completion (judged by TLC). The reaction was quenched with water and extracted with CH2Cl2 (3 × 100 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure and purified by flash column chromatography (CH2Cl2/ethyl acetate, 30:1 to 20:1) to afford sulfinamidine P2 as a white solid (6.23 g, 13.69 mmol, 87%). mp 118-120 °C (CH2Cl2); Rf 0.57 (CH2Cl2/ethyl acetate, 15:1); ¹ H NMR (400 MHz, CDCl3): δ (ppm) = 8.21 (d, J = 8.8 Hz, 2H), 7.96 (d, J = 8.8 Hz, 2H), 7.67- 7.47 (m, 2H), 7.19-6.89 (m, 2H), 4.48 (s, 1H), 1.65 (d, J = 15.0 Hz, 1H), 1.61 (d, J = 15.0 Hz, 1H), 1.48 (s, 3H), 1.44 (s, 3H), 0.97 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 164.7 (d, J = 254.7 Hz), 150.2, 149.2, 133.5 (d, J = 3.1 Hz), 129.4 (d, J = 9.1 Hz), 127.3, 124.0, 116.8 (d, J = 22.9 Hz), 60.6, 55.6, 31.8, 31.7, 30.7, 29.1; 19F NMR (377 MHz, CDCl3): δ (ppm) = -106.7 (tt, J = 8.0, 4.9 Hz); IR (ATR): ṽ (cm ^–1 ) = 1528, 1490, 1349, 1290, 1145, 1088, 982, 618; HRMS (ESI ⁺ ) calcd. for C20H27FN3O4S2 ⁺ [M+H] ⁺ : 456.1422, found: 456.1421. [00349] N-(S-(4-Chlorophenyl)-N-(2,4,4-trimethylpentan-2-yl)sulfinim idoyl)-4- nitrobenzenesulfonamide (P3) Prepared according to General Procedure A using N-sulfinyl-tert-octylamine (1.27 g, 7.23 mmol, 1.00 equiv.), THF (14.5 mL), LiHMDS (7.23 mL, 1.0 M in THF, 7.23 mmol, 1.00 equiv.), TMSCl (917 µL, 7.23 mmol, 1.00 equiv.), 4-chlorophenylmagnesium bromide solution (9.85 mL, 0.88 M in 2-methyltetrahydrofuran, 8.67 mmol, 1.20 equiv.), CH ₂ Cl ₂ (36.0 mL), Et ₃ N (1.21 mL, 8.68 mmol, 1.20 equiv.) and NsCl (1.76 mg, 7.95 mmol, 1.10 equiv.). Purification by flash column chromatography (CH2Cl2/ethyl acetate, 50:1 to 30:1 to 20:1) afforded sulfinamidine P3 as a white solid (3.01g, 6.39 mmol, 88%). mp 110-112 °C (CH ₂ Cl ₂ ); R _f 0.40 (petrol/ethyl acetate, 2:1); ¹ H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.23 (d, J = 8.9 Hz, 2H), 7.96 (d, J = 8.9 Hz, 2H), 7.54 (d, J = 8.8 Hz, 2H), 7.39 (d, J = 8.8 Hz, 2H), 4.49 (s, 1H), 1.67 (d, J = 14.9 Hz, 1H), 1.63 (d, J = 14.9 Hz, 1H), 1.51 (s, 3H), 1.47 (s, 3H), 0.99 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 150.2, 149.2, 138.7, 136.6, 129.8, 128.4, 127.3, 124.1, 60.7, 55.7, 31.81, 31.75, 30.7, 29.2 (note: for the gem-dimethyl carbons in the tert-octyl group, NC(CH3)2CH2C(CH3)3; IR (ATR): ṽ (cm ^–1 ) = 1527, 1349, 1290, 1145, 1088, 982, 745, 620; HRMS (ESI ⁺ ) calcd. for C20H27ClN3O4S2 ⁺ [M+H] ⁺ : 472.1126, found: 472.1125. [00350] N-(S-(3-Chlorophenyl)-N-(2,4,4-trimethylpentan-2-yl)sulfinim idoyl)-4- nitrobenzenesulfonamide (P4) Prepared according to General Procedure A using N-sulfinyl-tert-octylamine (1.23 g, 7.00 mmol, 1.00 equiv.), THF (14.0 mL), LiHMDS (7.00 mL, 1.0 M in THF, 7.00 mmol, 1.00 equiv.), TMSCl (888 µL, 7.00 mmol, 1.00 equiv.), 3-chlorophenyl magnesium chloride lithium chloride complex solution (8.40 mmol, 1.20 equiv.), CH ₂ Cl ₂ (35.0 mL), Et ₃ N (1.17 mL, 8.40 mmol, 1.20 equiv.) and NsCl (1.71 g, 7.70 mmol, 1.10 equiv.). Purification by flash column chromatography (CH ₂ Cl ₂ /ethyl acetate, 50:1 to 30:1) afforded sulfinamidine P4 as a white solid (2.15g, 4.56 mmol, 65%). mp 104-106 °C (CH ₂ Cl ₂ ); Rf 0.45 (CH ₂ Cl ₂ /ethyl acetate, 20:1); ¹ H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.23 (d, J = 8.8 Hz, 2H), 7.94 (d, J = 8.8 Hz, 2H), 7.52- 7.47 (m, 2H), 7.46-7.41 (m, 1H), 7.40-7.34 (m, 1H), 4.59 (s, 1H), 1.71 (d, J = 14.9 Hz, 1H), 1.66 (d, J = 14.9 Hz, 1H), 1.53 (s, 3H), 1.51 (s, 3H), 1.02 (s, 9H); 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 150.1, 149.3, 139.8, 135.8, 132.1, 130.7, 127.3, 127.2, 125.3, 124.1, 60.9, 55.7, 31.9, 31.8, 30.9, 29.4; IR (ATR): ṽ (cm ^–1 ) = 2980, 1527, 1462, 1383, 1349, 1290, 1251, 1147, 1087, 957, 855, 778, 732, 678, 618; HRMS (ESI ⁺ ) calcd. for C20H27ClN3O4S2 ⁺ [M+H] ⁺ : 472.1126, found: 472.1125. [00351] N-(S-(4-Cyanophenyl)-N-(2,4,4-trimethylpentan-2-yl)sulfinimi doyl)-4- nitrobenzenesulfonamide (P5) Prepared according to General Procedure A using N-sulfinyl-tert-octylamine (1.23 g, 7.00 mmol, 1.00 equiv.), THF (14.0 mL), LiHMDS (7.00 mL, 1.0 M in THF, 7.00 mmol, 1.00 equiv.), TMSCl (888 µL, 7.00 mmol, 1.0 equiv.), 4-cyanophenyl magnesium chloride lithium chloride complex solution (8.40 mmol, 1.20 equiv.), CH2Cl2 (35.0 mL), Et3N (1.17 mL, 8.40 mmol, 1.20 equiv.) and NsCl (1.71 g, 7.70 mmol, 1.10 equiv.). Purification by flash column chromatography (CH ₂ Cl ₂ /ethyl acetate, 25:1 to 15:1 to 10:1) afforded sulfinamidine P5 as a white solid (2.16 g, 4.68 mmol, 67%). mp 126-128 °C (CH ₂ Cl ₂ ); Rf 0.34 (CH ₂ Cl ₂ /ethyl acetate, 15:1); ¹ H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.27 (d, J = 8.8 Hz, 2H), 8.02 (d, J = 8.8 Hz, 2H), 7.82 (d, J = 8.8 Hz, 2H), 7.76 (d, J = 8.8 Hz, 2H), 4.54 (s, 1H), 1.68 (d, J = 14.9 Hz, 1H), 1.64 (d, J = 14.9 Hz, 1H), 1.51 (s, 3H), 1.46 (s, 3H), 1.00 (s, 9H); 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 149.9, 149.5, 143.7, 133.2, 128.0, 127.4, 124.2, 117.2, 116.0, 61.1, 55.8, 31.9, 31.8, 30.7, 29.4; IR (ATR): ṽ (cm ^–1 ) = 2980, 1527, 1349, 1289, 1144, 1087, 982, 855, 732, 618; HRMS (ESI ⁺ ) calcd. for C21H27N4O4S2 ⁺ [M+H] ⁺ : 463.1468, found: 463.1462. [00352] N-(S-(3-Cyanophenyl)-N-(2,4,4-trimethylpentan-2-yl)sulfinimi doyl)-4- nitrobenzenesulfonamide (P6) Prepared according to General Procedure A using N-sulfinyl-tert-octylamine (1.23 g, 7.00 mmol, 1.00 equiv.), THF (14.0 mL), LiHMDS (7.00 mL, 1.0 M in THF, 7.00 mmol, 1.00 equiv.), TMSCl (888 µL, 7.00 mmol, 1.00 equiv.), 3-cyanophenyl magnesium chloride lithium chloride complex solution (8.40 mmol, 1.20 equiv.), CH2Cl2 (35.0 mL), Et3N (1.17 mL, 8.40 mmol, 1.20 equiv.) and NsCl (1.71 g, 7.70 mmol, 1.10 equiv.). Purification by flash column chromatography (CH2Cl2/ethyl acetate, 25:1 to 15:1 to 10:1) afforded sulfinamidine P6 as a white solid (2.86 g, 6.19 mmol, 88%). mp 102-104 °C (CH2Cl2); Rf 0.57 (CH2Cl2/ethyl acetate, 15:1); ¹ H NMR (400 MHz, CDCl3): δ (ppm) = 8.27 (d, J = 8.9 Hz, 2H), 8.00 (d, J = 8.9 Hz, 2H), 7.93- 7.87 (m, 2H), 7.78 (dt, J = 7.7, 1.3 Hz, 1H), 7.60 (td, J = 7.7, 0.7 Hz, 1H), 4.66 (s, 1H), 1.69 (d, J = 14.9 Hz, 1H), 1.65 (d, J = 14.9 Hz, 1H), 1.51 (s, 3H), 1.47 (s, 3H), 1.01 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 149.9, 149.5, 140.6, 135.2, 131.4, 130.8, 130.5, 127.4, 124.2, 117.1, 114.2, 61.1, 55.7, 31.9, 31.8, 30.6, 29.4; IR (ATR): ṽ (cm ^–1 ) = 1527, 1349, 1291, 1145, 1087, 981, 855, 732, 684, 619; HRMS (ESI ⁺ ) calcd. for C ₂₁ H ₂₇ N ₄ O ₄ S ₂ ⁺ [M+H] ⁺ : 463.1468, found: 463.1463. [00353] N-(S-(4-Methoxyphenyl)-N-(2,4,4-trimethylpentan-2-yl)sulfini midoyl)-4- nitrobenzenesulfonamide (P7) Prepared according to General Procedure A using N-sulfinyl-tert-octylamine (1.26 g, 7.17 mmol, 1.00 equiv.), THF (14.3 mL), LiHMDS (7.17 mL, 1.0 M in THF, 7.23 mmol, 1.00 equiv.), TMSCl (910 µL, 7.17 mmol, 1.00 equiv.), 4-methoxyphenylmagnesium bromide solution (17.2 mL, 0.50 M in THF, 8.60 mmol, 1.20 equiv.), CH ₂ Cl ₂ (35.9 mL), Et ₃ N (1.20 mL, 8.60 mmol, 1.20 equiv.) and NsCl (1.75 g, 7.89 mmol, 1.10 equiv.). Purification by flash column chromatography (CH ₂ Cl ₂ /ethyl acetate, 30:1 to 20:1 to 10:1) afforded sulfinamidine P7 as a white solid (2.54 g, 5.44 mmol, 76%). mp 108-110 °C (CH2Cl2); Rf 0.2 (petrol /ethyl acetate, 2:1); ¹ H NMR (400 MHz, CDCl3): δ (ppm) = 8.19 (d, J = 8.8 Hz, 2H), 7.94 (d, J = 8.8 Hz, 2H), 7.48 (d, J = 9.0 Hz, 2H), 6.88 (d, J = 9.0 Hz, 2H), 4.35 (s, 1H), 3.80 (s, 3H), 1.68 (d, J = 15.0 Hz, 1H), 1.63 (d, J = 15.0 Hz, 1H), 1.52 (s, 3H), 1.49 (s, 3H), 1.00 (s, 9H): 13C NMR (101 MHz, CDCl3): δ (ppm) = 162.5, 150.5, 149.1, 128.7, 128.5, 127.3, 124.0, 114.9, 60.4, 55.8, 55.7, 31.83, 31.79, 30.9, 29.2; IR (ATR): ṽ (cm ^–1 ) = 1526, 1494, 1348, 1287, 1257, 1143, 1085, 1017, 980, 731, 616; HRMS (ESI ⁺ ) calcd. for C21H30N3O5S2 ⁺ [M+H] ⁺ : 468.1621, found: 468.1620. [00354] 4-Nitro-N-(S-(o-tolyl)-N-(2,4,4-trimethylpentan-2- yl)sulfinimidoyl)benzenesulfonamide (P8) Prepared according to General Procedure A using N-sulfinyl-tert-octylamine (1.23 g, 7.00 mmol, 1.00 equiv.), THF (14.0 mL), LiHMDS (7.00 mL, 1.0 M in THF, 7.00 mmol, 1.00 equiv.), TMSCl (888 µL, 7.00 mmol, 1.00 equiv.), 2-methylphenylmagnesium bromide solution (13.1 mL, 0.64 M in THF, 8.40 mmol, 1.20 equiv.), CH ₂ Cl ₂ (14.0 mL), Et ₃ N (1.95 mL, 14.00 mmol, 2.00 equiv.) and NsCl (2.33 g, 10.50 mmol, 1.50 equiv.). Purification by flash column chromatography (CH ₂ Cl ₂ /ethyl acetate, 60:1 to 30:1 to 20:1) afforded sulfinamidine P8 as a white solid (2.58 g, 5.72 mmol, 82%). mp 110-112 °C (CH2Cl2); R _f 0.36 (CH ₂ Cl ₂ /ethyl acetate, 30:1); ¹ H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.08 (d, J = 8.9 Hz, 2H), 7.94 (dd, J = 7.4, 1.9 Hz, 1H), 7.75 (d, J = 8.9 Hz, 2H), 7.38-7.29 (m, 2H), 7.09-7.05 (m, 1H), 4.49 (s, 1H), 2.36 (s, 3H), 1.70 (d, J = 14.9 Hz, 1H), 1.65 (d, J = 14.9 Hz, 1H), 1.57 (s, 3H), 1.51 (s, 3H), 0.99 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 150.1, 148.9, 136.6, 136.2, 132.3, 131.6, 127.2, 127.1, 125.6, 123.7, 60.8, 55.7, 31.82, 31.75, 30.5, 29.2, 19.4;IR (ATR): ṽ (cm ^–1 ) = 2980, 1526, 1348, 1286, 1143, 1088, 968, 731, 616; HRMS (ESI ⁺ ) calcd. for C21H30N3O4S2 ⁺ [M+H] ⁺ : 452.1672, found: 452.1669. [00355] N-(S-(3,5-Difluorophenyl)-N-(2,4,4-trimethylpentan-2-yl)sulf inimidoyl)-4- nitrobenzenesulfonamide (P9) Prepared according to General Procedure A using N-sulfinyl-tert-octylamine (1.02 g, 5.82 mmol, 1.00 equiv.), THF (11.6 mL), LiHMDS (5.82 mL, 1.0 M in THF, 5.82 mmol, 1.00 equiv.), TMSCl (739 µL, 5.82 mmol, 1.00 equiv.), 3,5-difluorophenylmagnesium bromide solution (29.1 mL, 0.24 M in THF, 6.98 mmol, 1.20 equiv.), CH ₂ Cl ₂ (29.1 mL), Et ₃ N (973 µL, 6.98 mmol, 1.20 equiv.) and NsCl (1.42 g, 6.40 mmol, 1.10 equiv.). Purification by flash column chromatography (CH ₂ Cl ₂ /ethyl acetate, 50:1 to 25:1) afforded sulfinamidine P9 as a white solid (2.36 g, 4.99 mmol, 86%). mp 110-112 °C (CH ₂ Cl ₂ ); Rf 0.50 (CH ₂ Cl ₂ /ethyl acetate, 25:1); ¹ H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.26 (d, J = 8.9 Hz, 2H), 7.99 (d, J = 8.9 Hz, 2H), 7.15 (ddd, J = 5.6, 2.3, 1.0 Hz, 2H), 6.92 (tt, J = 8.3, 2.3 Hz, 1H), 4.68 (s, 1H), 1.69 (d, J = 14.9 Hz, 1H), 1.65 (d, J = 14.9 Hz, 1H),1.50 (s, 3H), 1.47 (s, 3H), 1.01 (s, 9H);13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 163.0 (dd, J = 255.2, 11.8 Hz), 149.9, 149.4, 142.2 (t, J = 8.5 Hz), 127.4, 124.2, 111.8-110.2, 107.6 (t, J = 25.1 Hz), 61.1, 55.7, 31.83, 31.75, 30.6, 29.3; 19F NMR (377 MHz, CDCl ₃ ): δ (ppm) = -104.7 – -104.8; IR (ATR): ṽ (cm ^–1 ) = 1600, 1528, 1437, 1349, 1291, 1146, 1125, 1088, 990, 855, 731, 619; HRMS (ESI ⁺ ) calcd. for C20H26F2N3O4S2 ⁺ [M+H] ⁺ : 474.1327, found: 474.1319. [00356] N-(6-Methoxy-N-(2,4,4-trimethylpentan-2-yl)pyridine-3-sulfin imidoyl)-4- nitrobenzenesulfonamide (P10) Preparation of organometallic reagent (6-Methoxypyridin-3-yl)lithium solution was prepared according to the following procedure. To a solution of 5-bromo-2-methoxypyridine (1.74 g, 9.25 mmol, 1.20 equiv.) in anhydrous THF (18.5 mL) in an oven-dried 100 mL round-bottom flask was added n-butyllithium solution (3.70 mL, 2.50 M in hexanes, 9.25 mmol, 1.20 equiv.) dropwise at -78 °C. The reaction was stirred at the same temperature for 40 min. Preparation of sulfinamidine Prepared according to General Procedure A using N-sulfinyl-tert-octylamine (1.35 g, 7.71 mmol, 1.00 equiv.), THF (15.4 mL), LiHMDS (7.71 mL, 1.0 M in THF, 7.71 mmol, 1.00 equiv.), TMSCl (978 µL, 7.71 mmol, 1.00 equiv.), (6-methoxypyridin-3-yl)lithium solution (9.25 mmol, 1.20 equiv.), CH ₂ Cl ₂ (38.5 mL), Et ₃ N (1.29 mL, 9.25 mmol, 1.20 equiv.) and NsCl (1.88 mg, 8.47 mmol, 1.10 equiv.). Purification by flash column chromatography (CH ₂ Cl ₂ /ethyl acetate, 25:1 to 15:1 to 5:1) afforded sulfinamidine P10 as a white solid (2.89 g, 6.18 mmol, 80%). mp 120-122 °C (CH ₂ Cl ₂ ); R _f 0.38 (CH ₂ Cl ₂ /ethyl acetate, 10:1); ¹ H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.28 (dd, J = 2.7, 0.7 Hz, 1H), 8.21 (d, J = 8.8 Hz, 2H), 7.94 (d, J = 8.8 Hz, 2H), 7.71 (dd, J = 8.9, 2.7 Hz, 1H), 6.73 (dd, J = 8.9, 0.7 Hz, 1H), 4.60 (s, 1H), 3.91 (s, 3H), 1.66 (d, J = 15.0 Hz, 1H), 1.64 (d, J = 15.0 Hz, 1H), 1.51 (s, 3H), 1.48 (s, 3H), 1.00 (s, 9H); 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 166.3, 150.2, 149.2, 146.7, 137.0, 127.3, 126.7, 124.1, 112.0, 60.7, 55.6, 54.4, 31.82, 31.76, 30.7, 29.3; IR (ATR): ṽ (cm ^–1 ) = 1588, 1527, 1478, 1371, 1349, 1285, 1145, 1087, 1015, 979, 732, 619; HRMS (ESI ⁺ ) calcd. for C ₂₀ H ₂₉ N ₄ O ₅ S ₂ ⁺ [M+H] ⁺ : 469.1574, found: 469.1570. [00357] 4-Nitro-N-(N-(2,4,4-trimethylpentan-2-yl)pyridine-3- sulfinimidoyl)benzenesulfonamide (P11) Preparation of organometallic reagent 3-Pyridylmagnesium chloride lithium chloride complex solution was prepared according to the following procedure. To a solution of 3-bromopyridine (1.32 g, 8.40 mmol, 1.20 equiv.) in anhydrous THF (8.4 mL) in an oven-dried 100 mL round-bottom flask was added isopropyl magnesium chloride lithium chloride complex solution (Turbo Grignard Reagent) (6.83 mL, 8.40 mmol, 1.23 M in THF, 1.20 equiv.) dropwise at 0 °C . The reaction was stirred at 0 °C for 1 h. Then the mixture was warmed to room temperature and stirred for another 0.5 h. Preparation of sulfinamidine Prepared according to General Procedure A using N-sulfinyl-tert-octylamine (1.23 g, 7.00 mmol, 1.00 equiv.), THF (14.0 mL), LiHMDS (7.00 mL, 1.0 M in THF, 7.00 mmol, 1.00 equiv.), TMSCl (888 µL, 7.00 mmol, 1.0 equiv.), 3-pyridylmagnesium chloride lithium chloride complex solution (8.40 mmol, 1.20 equiv.), CH ₂ Cl ₂ (35.0 mL), Et ₃ N (1.17 mL, 8.40 mmol, 1.20 equiv.) and NsCl (1.71 g, 7.70 mmol, 1.10 equiv.). Purification by flash column chromatography (CH ₂ Cl ₂ /ethyl acetate, 5:1 to 1:1 to 1:2) afforded sulfinamidine P11 as a white solid (2.31 g, 5.27 mmol, 75%). mp 114-116 °C (CH ₂ Cl ₂ ); Rf 0.26 (CH ₂ Cl ₂ /ethyl acetate, 1:1); ¹ H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.76 (s, 1H), 8.67 (d, J = 4.8 Hz, 1H), 8.23 (d, J = 8.8 Hz, 2H), 7.98 (d, J = 8.8 Hz, 2H), 7.97-7.93 (m, 1H), 7.38 (dd, J = 8.3, 4.8 Hz, 1H), 4.82 (s, 1H), 1.70 (d, J = 15.0 Hz, 1H), 1.65 (d, J = 15.0 Hz, 1H), 1.52 (s, 3H), 1.48 (s, 3H), 1.00 (s, 9H); 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 152.4, 149.9, 149.3, 148.1, 135.3, 135.1, 127.3, 124.2, 124.1, 61.0, 55.6, 31.8, 31.7, 30.7, 29.3; IR (ATR): ṽ (cm ^–1 ) =2980, 1526, 1349, 1289, 1145, 1087, 974, 731, 616; HRMS (ESI ⁺ ) calcd. for C ₁₉ H ₂₇ N ₄ O ₄ S ₂ ⁺ [M+H] ⁺ : 439.1368, found: 439.1469. [00358] N-(S-Cyclopropyl-N-(2,4,4-trimethylpentan-2-yl)sulfinimidoyl )-4- nitrobenzenesulfonamide (P12) Prepared according to General Procedure A using N-sulfinyl-tert-octylamine (1.21 g, 6.91 mmol, 1.00 equiv.), THF (13.8 mL), LiHMDS (6.91 mL, 1.0 M in THF, 6.91 mmol, 1.00 equiv.), TMSCl (876 µL, 6.91 mmol, 1.00 equiv.), cyclopropylmagnesium bromide solution (9.87 mL, 0.84 M in 2-methyltetrahydrofuran, 8.29 mmol, 1.20 equiv.), CH2Cl2 (34.5 mL), Et3N (1.16 mL, 8.29 mmol, 1.20 equiv.) and NsCl (1.68 g, 7.59 mmol, 1.10 equiv.). Purification by flash column chromatography (petrol/ethyl acetate, 3:1 to 1:1) afforded sulfinamidine P12 as a white solid (2.32 g, 5.79 mmol, 84%). mp 122-124 °C (CH2Cl2); Rf 0.44 (petrol/ethyl acetate, 1:1); 1H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.27 (d, J = 8.9 Hz, 2H), 8.03 (d, J = 8.9 Hz, 2H), 4.10 (s, 1H), 2.50 (tt, J = 7.8, 4.7 Hz, 1H), 1.57 (d, J = 15.0 Hz, 1H), 1.52 (d, J = 15.0 Hz, 1H), 1.39 (s, 3H), 1.35 (s, 3H), 1.24 (ddt, J = 11.3, 6.6, 4.9 Hz, 1H), 0.98 (s, 9H), 0.92-0.77 (m, 2H), 0.63-0.55 (m, 1H); 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 150.8, 149.2, 127.4, 124.1, 59.6, 55.4, 31.9, 31.7, 31.1, 30.9, 28.9, 4.6, 1.7; IR (ATR): ṽ (cm ^–1 ) = 1526, 1349, 1285, 1142, 1089, 981, 855, 731, 616; HRMS (ESI ⁺ ) calcd. for C ₁₇ H ₂₈ N ₃ O ₄ S ₂ ⁺ [M+H] ⁺ : 402.1516, found: 402.1514. [00359] N-(S-Ethyl-N-(2,4,4-trimethylpentan-2-yl)sulfinimidoyl)-4- nitrobenzenesulfonamide (P13) Prepared according to General Procedure A using N-sulfinyl-tert-octylamine (1.34 g, 7.62 mmol, 1.00 equiv.), THF (15.2 mL), LiHMDS (7.62 mL, 1.0 M in THF, 7.62 mmol, 1.00 equiv.), TMSCl (967 µL, 7.62 mmol, 1.00 equiv.), ethylmagnesium bromide solution (9.62 mL, 0.95 M in THF, 9.14 mmol, 1.20 equiv.), CH2Cl2 (38.1 mL), Et3N (1.28 mL, 9.14 mmol, 1.20 equiv.) and NsCl (1.86 g, 8.38 mmol, 1.10 equiv.). Purification by flash column chromatography (CH2Cl2/ethyl acetate, 20:1 to 5:1) afforded sulfinamidine P13 as a white solid (1.80 g, 4.63 mmol, 61%). mp 122-124 °C (CH2Cl2); Rf 0.50 (CH2Cl2/ethyl acetate, 4:1); ¹ H NMR (400 MHz, CDCl3): δ (ppm) = 8.27 (d, J = 8.9 Hz, 2H), 8.05 (d, J = 8.8 Hz, 2H), 4.41 (s, 1H), 3.15 (q, J = 7.4 Hz, 2H), 1.58 (d, J = 14.9 Hz, 1H), 1.53 (d, J = 14.9 Hz, 1H), 1.39 (s, 3H), 1.36 (s, 3H), 1.15 (t, J = 7.4 Hz, 3H), 0.97 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 150.7, 149.3, 127.3, 124.1, 59.8, 55.6, 48.8, 31.8, 31.7, 31.0, 28.8, 8.8; IR (ATR): ṽ (cm ^–1 ) =1527, 1349, 1285, 1142, 1089, 979, 855, 744, 615; HRMS (ESI ⁺ ) calcd. for C16H28N3O4S2 ⁺ [M+H] ⁺ : 390.1516, found: 390.1518. [00360] 4-Nitro-N-(N-(2,4,4-trimethylpentan-2-yl)-S- vinylsulfinimidoyl)benzenesulfonamide (P14) Prepared according to General Procedure A using N-sulfinyl-tert-octylamine (1.31 g, 7.50 mmol, 1.00 equiv.), THF (15.0 mL), LiHMDS (7.50 mL, 1.0 M in THF, 7.50 mmol, 1.00 equiv.), TMSCl (952 µL, 7.50 mmol, 1.00 equiv.), vinylmagnesium bromide solution (10.1 mL, 0.89 M in THF, 8.99 mmol, 1.20 equiv.), CH ₂ Cl ₂ (37.5 mL), Et ₃ N (1.25 mL, 8.99 mmol, 1.20 equiv.) and NsCl (1.83 g, 8.25 mmol, 1.10 equiv.). Purification by flash column chromatography (CH ₂ Cl ₂ /ethyl acetate, 20:1 to 5:1) afforded sulfinamidine P14 as a white solid (2.04 g, 5.27 mmol, 70%). mp 92-94 °C (CH ₂ Cl ₂ ); Rf 0.30 (CH2Cl2/ethyl acetate, 10:1); ¹ H NMR (400 MHz, CDCl3): δ (ppm) = 8.27 (d, J = 8.9 Hz, 2H), 8.03 (d, J = 8.9 Hz, 2H), 6.50 (dd, J = 16.0, 9.2 Hz, 1H), 5.99 (dd, J = 16.0, 1.4 Hz, 1H), 5.90 (dd, J = 9.2, 1.4 Hz, 1H), 4.31 (s, 1H), 1.62 (d, J = 15.0 Hz, 1H), 1.54 (d, J = 15.0 Hz, 1H), 1.43 (s, 3H), 1.39 (s, 3H), 0.98 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 150.4, 149.3, 135.3, 127.3, 125.8, 124.1, 60.1, 55.3, 31.8, 31.7, 31.0, 29.1; IR (ATR): ṽ (cm ^–1 ) = 1526, 1349, 1287, 1143, 1088, 979, 855, 618; HRMS (ESI ⁺ ) calcd. for C16H26N3O4S2 ⁺ [M+H] ⁺ : 388.1359, found: 388.1361. [00361] N-(S-(3-Cyano-4-ethoxyphenyl)-N-(2,4,4-trimethylpentan-2- yl)sulfinimidoyl)-4-nitrobenzenesulfonamide (P15) Preparation of organometallic reagent (3-Cyano-4-ethoxyphenyl)lithium solution was prepared according to the following procedure. To a solution of 5-bromo-2-ethoxybenzonitrile (9.08 g, 40.3 mmol, 1.50 equiv.) in anhydrous THF (40.3 mL) in an oven-dried 100 mL round-bottom flask was added n-butyllithium solution (16.67 mL, 40.3 mmol, 2.42 M in hexanes, 1.50 equiv.) dropwise at -78 °C. The reaction was stirred at the same temperature for 20 min. Preparation of sulfinamidine Prepared according to General Procedure A using N-sulfinyl-tert-octylamine (4.73 g, 27.00 mmol, 1.00 equiv.), THF (27.0 mL), LiHMDS (27.00 mL, 1.0 M in THF, 27.00 mmol, 1.00 equiv.), TMSCl (3.43 mL, 27.00 mmol, 1.0 equiv.), (3-cyano-4-ethoxyphenyl)lithium solution (40.3 mmol, 1.50 equiv.), CH ₂ Cl ₂ (135.0 mL), Et ₃ N (6.02 mL, 43.20 mmol, 1.60 equiv.) and NsCl (8.98 g, 40.50 mmol, 1.50 equiv.). Purification by flash column chromatography (CH ₂ Cl ₂ /ethyl acetate, 20:1 to 10:1) afforded sulfinamidine P15 as a white solid (7.11 g, 14.05 mmol, 52%). mp 128-130 °C (CH ₂ Cl ₂ ); Rf 0.50 (CH2Cl2/ethyl acetate, 9:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.25 (d, J = 8.9 Hz, 2H), 7.99 (d, J = 8.9 Hz, 2H), 7.78- 7.73 (m, 2H), 6.99 (d, J = 8.9 Hz, 1H), 4.54 (s, 1H), 4.18 (qd, J = 7.0, 1.0 Hz, 2H), 1.67 (d, J = 15.0 Hz, 1H), 1.63 (d, J = 15.0 Hz, 1H), 1.50 (s, 3H), 1.49 (t, J = 7.0 Hz, 3H), 1.46 (s, 3H), 1.00 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 163.1, 150.1, 149.4, 133.2, 132.8, 129.9, 127.4, 124.2, 114.8, 113.0, 103.6, 65.9, 60.8, 55.7, 31.84, 31.76, 30.7, 29.4, 14.4; IR (ATR): ṽ (cm ^–1 ) = 2981, 1528, 1473, 1383, 1349, 1286, 1252, 1147, 1087, 956; HRMS (ESI ⁺ ) calcd. for C23H31N4O5S2 ⁺ [M+H] ⁺ : 507.1730, found: 507.1729. [00362] 4-Nitro-N-(S-(4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol- 1-yl)phenyl)-N- (2,4,4-trimethylpentan-2-yl)sulfinimidoyl)benzenesulfonamide (P16) Preparation of organometallic reagent (4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)l ithium solution was prepared according to the following procedure. To a solution of 1-(4-bromophenyl)-5-(p-tolyl)-3- (trifluoromethyl)-1H-pyrazole (2.42 g, 6.37 mmol, 1.20 equiv.) in anhydrous THF (12.7 mL) in an oven-dried 100 mL round-bottom flask was added n-butyllithium solution (2.55 mL, 6.37 mmol, 2.50 M in hexanes, 1.20 equiv.) dropwise at -78 °C. The reaction was stirred at the same temperature for 40 min. Preparation of sulfinamidine Prepared according to General Procedure A using N-sulfinyl-tert-octylamine (0.92 g, 5.22 mmol, 1.00 equiv.), THF (10.4 mL), LiHMDS (5.22 mL, 1.0 M in THF, 5.22 mmol, 1.00 equiv.), TMSCl (663 µL, 5.22 mmol, 1.00 equiv.), (4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1- yl)phenyl)lithium solution (6.37 mmol, 1.20 equiv.), CH2Cl2 (26.1 mL), Et3N (888 µL, 6.37 mmol, 1.20 equiv.) and NsCl (1.27 g, 5.74 mmol, 1.10 equiv.). Purification by flash column chromatography (CH2Cl2/ethyl acetate, 50:1 to 30:1 to 20:1) afforded P16 as a white solid (3.28 g, 4.96 mmol, 95%). mp 95-97 °C (CH2Cl2); Rf 0.45 (CH2Cl2/ethyl acetate, 30:1); 1H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.22 (d, J = 8.8 Hz, 2H), 7.99 (d, J = 8.8 Hz, 2H), 7.61 (d, J = 8.9 Hz, 2H), 7.40 (d, J = 8.9 Hz, 2H), 7.15 (d, J = 8.0 Hz, 2H), 7.07 (d, J = 8.0 Hz, 2H), 6.71 (s, 1H), 4.46 (s, 1H), 2.37 (s, 3H), 1.66 (d, J = 15.0 Hz, 1H), 1.62 (d, J = 15.0 Hz, 1H), 1.50 (s, 3H), 1.44 (s, 3H), 0.98 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 150.1, 149.3, 145.3, 144.2 (q, J = 38.5 Hz), 142.2, 140.0, 137.7, 129.8, 128.8, 128.0, 127.4, 125.78, 125.75, 124.1, 121.10 (q, J = 269.3 Hz), 106.5, 60.8, 55.8, 31.8, 31.7, 30.7, 29.2, 21.4; 19F NMR (377 MHz, CDCl3): δ (ppm) = -62.4 (s); IR (ATR): ṽ (cm ^–1 ) = 1528, 1349, 1236, 1139, 1088, 969, 855, 732, 614; HRMS (ESI ⁺ ) calcd. for C31H35F3N5O4S2 ⁺ [M+H] ⁺ : 662.2077, found: 662.2071. [00363] General Procedure B - Sulfondiimidoyl Fluoride Synthesis Sulfinamidine (1.00 equiv.) and NaH (60 % dispersion in mineral oil, 1.10 equiv.) were added to an oven-dried round-bottom flask at 0 °C and the flask was purged with nitrogen gas. Anhydrous THF (0.5 M) was added, and the reaction was stirred at 0 °C for 5 min before being warmed to room temperature and stirred for a further 25 min. NFSI (1.50 equiv.) was then added under a positive pressure of nitrogen and the reaction was stirred at room temperature for 30 min before being quenched with sat. aq. NaCl solution. Ethyl acetate was added, and the organic layers was separated. The aqueous layers was further extracted with ethyl acetate. The combined organic extracts were dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give a yellow solid. Diethyl ether was added to the crude yellow solid and the resulting suspension was shaken well before being filtered. The white filter cake was washed with further diethyl ether, and the combined filtrate was concentrated under reduced pressure to give a crude product containing a mixture of N-fluorinated product and S- fluorinated product. The crude product was allowed to stand at room temperature (open to air) for 1-8 days until all the N-fluorinated product had isomerized to the desired S-fluorinated product (as determined by TLC and NMR). The crude product was then purified by flash column chromatography to afford the sulfondiimidoyl fluoride. The time taken for the N-fluorinated compound to isomerize into the S-fluorinated compound varies from substrate to substrate. ¹⁹ F NMR can be used to monitor this isomerization reaction and determine when it is complete. The chemical shift of the fluorine atom of N-fluorinated compound in the ¹⁹ F NMR is usually around 80 ppm, and the chemical shift of the fluorine atom of S-fluorinated compound in the ¹⁹ F NMR is usually around -70 ppm. [00364] 4-Fluoro-N-((4-nitrophenyl)sulfonyl)-N-(2,4,4-trimethylpenta n-2- yl)benzenesulfondiimidoyl fluoride (P17) Sulfinamidine P2 (2.20 g, 4.84 mmol, 1.00 equiv.) and NaH (213 mg, 60 % dispersion in mineral oil, 5.32 mmol, 1.10 equiv.) were added to an oven-dried 100 mL round-bottom flask at 0 °C and the flask was purged with nitrogen gas. Anhydrous THF (9.70 mL) was added, and the reaction was stirred at 0 °C for 5 min before being warmed to room temperature and stirred for a further 25 min. NFSI (2.29 g, 7.26 mmol, 1.50 equiv.) was then added under a positive pressure of nitrogen and the reaction was stirred at room temperature for 30 min before being quenched with sat. aq. NaCl solution (250 mL).. Ethyl acetate (150 mL) was added, and the organic layers was separated. The aqueous layers was further extracted with ethyl acetate (2 × 60 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a yellow solid. Diethyl ether (250 ml) was added to the crude yellow solid and the resulting suspension was shaken well before being filtered. The white filter cake was washed with further diethyl ether (100 ml), and the combined filtrate was concentrated under reduced pressure to give a crude product containing a mixture of N-fluorinated product and S-fluorinated product. The crude product was allowed to stand at room temperature (open to air) for 20 h until all the N-fluorinated product had isomerized to the desired S-fluorinated product (as determined by TLC and NMR). The crude product was then purified by flash column chromatography (petrol/ethyl acetate, 4:1) to afford sulfondiimidoyl fluoride P17 as a pale-yellow solid (1.56 g, 3.30 mmol, 68%). mp 57-59 °C (CH2Cl2); Rf 0.59 (petrol/ethyl acetate, 6:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.32 (d, J = 8.9 Hz, 2H), 8.06 (d, J = 8.9 Hz, 2H), 8.04- 7.98 (m, 2H), 7.26-7.19 (m, 2H), 1.67 (d, J = 14.7 Hz, 1H), 1.52 (d, J = 14.7 Hz, 1H), 1.48 (s, 3H), 1.43 (s, 3H), 0.96 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 166.1 (d, J = 258.8 Hz), 150.0, 148.3, 134.4 (dd, J = 25.1, 3.3 Hz), 130.6 (d, J = 9.8 Hz), 128.1, 124.2, 116.9 (d, J = 23.1 Hz), 63.5 (d, J = 4.6 Hz), 56.5 (d, J = 3.2 Hz), 31.84, 31.79 (d, J = 2.7 Hz), 31.52, 31.45 (d, J = 6.6 Hz); 19F NMR (377 MHz, CDCl3): δ (ppm) = 86.5 (s), -101.4 (tt, J = 7.8, 4.7 Hz); IR (ATR): ṽ (cm ^–1 ) = 2980, 1532, 1492, 1348, 1240, 1163, 1089, 1075; HRMS (ESI ⁺ ) calcd. for C20H25F2N3O4S2Na ⁺ [M+Na] ⁺ : 496.1147, found: 496.1146. [00365] 4-Chloro-N-((4-nitrophenyl)sulfonyl)-N-(2,4,4-trimethylpenta n-2- yl)benzenesulfondiimidoyl fluoride (P18) Prepared according to General Procedure B using P3 (707 mg, 1.50 mmol, 1.00 equiv.), THF (3.00 mL), NaH (66.0 mg, 60 % dispersion in mineral oil, 1.65 mmol, 1.10 equiv.) and NFSI (709 mg, 2.25 mmol, 1.50 equiv.). The N to S fluoride migration took 16 h at room temperature for this substrate. Purification by flash column chromatography (petrol/ethyl acetate, 4:1) afforded sulfondiimidoyl fluoride P18 as a white solid (520 mg, 1.06 mmol, 71%). mp 66-68 °C (CH ₂ Cl ₂ ); Rf 0.55 (petrol /ethyl acetate, 3:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.32 (d, J = 8.9 Hz, 2H), 8.06 (d, J = 8.9 Hz, 2H), 7.92 (d, J = 8.9 Hz, 2H), 7.52 (d, J = 8.9 Hz, 2H), 1.67 (d, J = 14.7 Hz, 1H), 1.53 (d, J = 14.7 Hz, 1H), 1.48 (s, 3H), 1.44 (s, 3H), 0.97 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 150.0, 148.2, 141.4, 136.9 (d, J = 25.3 Hz), 129.8, 129.0, 128.1, 124.2, 63.5 (d, J = 4.4 Hz), 56.5 (d, J = 3.4 Hz), 31.83, 31.81 (d, J = 2.5 Hz), 31.51, 31.46 (d, J = 5.9 Hz); 19F NMR (377 MHz, CDCl3): δ (ppm) = 86.0 (s); IR (ATR): ṽ (cm ^–1 ) = 1531, 1347, 1309, 1162, 1108, 1087, 1072, 1010, 745, 610; HRMS (ESI ⁺ ) calcd. for C20H25ClFN3O4S2Na ⁺ [M+Na] ⁺ : 512.0851, found: 512.0861. [00366] 3-Chloro-N-((4-nitrophenyl)sulfonyl)-N-(2,4,4-trimethylpenta n-2- yl)benzenesulfondiimidoyl fluoride (P19) Prepared according to General Procedure B using P4 (471 mg, 1.00 mmol, 1.00 equiv.), THF (2.00 mL), NaH (44.0 mg, 60 % dispersion in mineral oil, 1.10 mmol, 1.10 equiv.) and NFSI (473 mg, 1,50 mmol, 1.50 equiv.). The N to S fluoride migration took 24 h at room temperature for this substrate. Purification by flash column chromatography (petrol/ethyl acetate, 4:1) afforded sulfondiimidoyl fluoride P19 as a pale-yellow oil (313 mg, 0.64 mmol, 64%). R _f 0.70 (petrol/ethyl acetate, 3:1); 1H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.29 (d, J = 8.9 Hz, 2H), 8.02 (d, J = 8.9 Hz, 2H), 7.87 (ddd, J = 8.1, 2.0, 1.0 Hz, 1H), 7.81 (t, J = 2.0 Hz, 1H), 7.61 (ddd, J = 8.1, 2.0, 1.0 Hz, 1H), 7.49 (t, J = 8.1 Hz, 1H), 1.68 (d, J = 14.7 Hz, 1H), 1.54 (d, J = 14.7 Hz, 1H), 1.51 (s, 3H), 1.47 (s, 3H), 0.97 (s, 9H); 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 150.0, 148.0, 139.7 (d, J = 25.3 Hz), 135.5, 134.5, 130.7, 128.1, 127.4, 125.7, 124.2, 63.7 (d, J = 4.6 Hz), 56.4 (d, J = 3.3 Hz), 31.84 (d, J = 2.8 Hz), 31.78, 31.5, 31.4; 19F NMR (377 MHz, CDCl3): δ (ppm) = 85.8 (s); IR (ATR): ṽ (cm ^–1 ) = 2980.1531, 1347, 1310.1163, 1131, 1088, 1071, 672, 616; HRMS (ESI ⁺ ) calcd. for C20H25ClFN3O4S2Na ⁺ [M+Na] ⁺ : 512.0851, found: 512.0854. [00367] 4-Cyanophenyl-N-((4-nitrophenyl)sulfonyl)-N-(2,4,4-trimethyl pentan-2- yl)benzenesulfondiimidoyl fluoride (P20) Prepared according to General Procedure B using P5 (693 mg, 1.50 mmol, 1.00 equiv.), THF (3.00 mL), NaH (66.0 mg, 60 % dispersion in mineral oil, 1.65 mmol, 1.10 equiv.) and NFSI (709 mg, 2.25 mmol, 1.50 equiv.). The N to S fluoride migration took 24 h at room temperature for this substrate. Purification by flash column chromatography (petrol /ethyl acetate, 4:1 to 3:1) afforded sulfondiimidoyl fluoride P20 as a colourless oil (325 mg, 0.68 mmol, 45%). Rf 0.50 (petrol/ethyl acetate, 3:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.34 (d, J = 8.8 Hz, 2H), 8.14 (d, J = 8.7 Hz, 2H), 8.08 (d, J = 8.8 Hz, 2H), 7.87 (d, J = 8.7 Hz, 2H), 1.66 (d, J = 14.7 Hz, 1H), 1.52 (d, J = 14.7 Hz, 1H), 1.47 (s, 3H), 1.43 (s, 3H), 0.95 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 150.1, 147.9, 142.5 (d, J = 26.3 Hz), 133.2, 128.2, 128.1, 124.3, 118.1, 116.8, 64.0 (d, J = 4.6 Hz), 56.3 (d, J = 3.3 Hz), 31.80, 31.78, 31.5, 31.4; 19F NMR (377 MHz, CDCl3): δ (ppm) = 86.3 (s); IR (ATR): ṽ (cm ^–1 ) = 2981, 1532, 1350, 1303, 1164, 1133, 1107, 1089, 1071; HRMS (ESI ⁺ ) calcd. for C21H25FN4O4S2Na ⁺ [M+Na] ⁺ : 503.1193, found: 503.1194. [00368] 3-Cyanophenyl-N-((4-nitrophenyl)sulfonyl)-N-(2,4,4-trimethyl pentan-2- yl)benzenesulfondiimidoyl fluoride (P21) Prepared according to General Procedure B using P6 (693 mg, 1.50 mmol, 1.00 equiv.), THF (3.00 mL), NaH (66.0 mg, 60 % dispersion in mineral oil, 1.65 mmol, 1.10 equiv.) and NFSI (709 mg, 2.25 mmol, 1.50 equiv.). The N to S fluoride migration took 24 h at room temperature for this substrate. Purification by flash column chromatography (petrol /ethyl acetate, 4:1 to 3:1) afforded P21 as a colourless oil (359 mg, 0.75 mmol, 50%). Rf 0.55 (petrol/ethyl acetate, 3:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.33 (d, J = 8.9 Hz, 2H), 8.27-8.21 (m, 2H), 8.07 (d, J = 8.9 Hz, 2H), 7.96 (dt, J = 7.8, 1.3 Hz, 1H), 7.73 (t, J = 7.8 Hz, 1H), 1.67 (d, J = 14.8 Hz, 1H), 1.54 (d, J = 14.8 Hz, 1H), 1.48 (s, 3H), 1.44 (s, 3H), 0.95 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 150.1, 147.8, 140.1 (d, J = 26.9 Hz), 137.3, 131.3, 131.1, 130.6, 128.1, 124.3, 116.6, 114.2, 64.0 (d, J = 4.6 Hz), 56.3 (d, J = 3.3 Hz), 31.8, 31.7, 31.5, 31.4; 19F NMR (377 MHz, CDCl3): δ (ppm) = 86.7 (s); IR (ATR): ṽ (cm ^–1 ) = 1532, 1349, 1306, 1164, 1109, 1087, 1073; HRMS (ESI ⁺ ) calcd. for C21H25FN4O4S2Na ⁺ [M+Na] ⁺ : 503.1193, found: 503.1188. [00369] 4-Methoxyphenyl-N-((4-nitrophenyl)sulfonyl)-N-(2,4,4-trimeth ylpentan-2- yl)benzenesulfondiimidoyl fluoride (P22) Prepared according to General Procedure B using P7 (467 mg, 1.00 mmol, 1.00 equiv.), THF (2.00 mL), NaH (44.0 mg, 60 % dispersion in mineral oil, 1.10 mmol, 1.10 equiv.) and NFSI (473 mg, 1.50 mmol, 1.50 equiv.). The N to S fluoride migration took 24 h at room temperature for this substrate. Purification by flash column chromatography (petrol/ethyl acetate, 4:1 to 3:1) afforded P22 as a colourless oil (325 mg, 0.67 mmol, 67%). R _f 0.54 (petrol/ethyl acetate, 3:1); 1H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.25 (d, J = 8.7 Hz, 2H), 8.00 (d, J = 8.7 Hz, 2H), 7.84 (d, J = 9.0 Hz, 2H), 6.93 (d, J = 9.0 Hz, 2H), 3.83 (s, 3H), 1.65 (d, J = 14.8 Hz, 1H), 1.51 (d, J = 14.8 Hz, 1H), 1.48 (s, 3H), 1.43 (s, 3H), 0.95 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 164.2, 149.7, 148.4, 129.9, 129.2 (d, J = 24.0 Hz), 128.0, 124.0, 114.5, 62.9 (d, J = 4.4 Hz), 56.4 (d, J = 3.2 Hz), 55.9, 31.72, 31.69 (d, J = 2.7 Hz), 31.5, 31.3 (d, J = 6.2 Hz); 19F NMR (377 MHz, CDCl3): δ (ppm) = 86.1 (s); IR (ATR): ṽ (cm ^–1 ) = 2981, 1531, 1349, 1311, 1266, 1162, 1104, 1089;HRMS (ESI ⁺ ) calcd. for C21H28FN3O5S2Na ⁺ [M+Na] ⁺ : 508.1347, found: 508.1353. [00370] Tolyl-N-((4-nitrophenyl)sulfonyl)-N-(2,4,4-trimethylpentan-2 - yl)benzenesulfondiimidoyl fluoride (P23) Prepared according to General Procedure B using P8 (451 mg, 1.00 mmol, 1.00 equiv.), THF (2.00 mL), NaH (44.0 mg, 60 % dispersion in mineral oil, 1.10 mmol, 1.10 equiv.) and NFSI (473 mg, 1.50 mmol, 1.50 equiv.). The N to S fluoride migration took 48 h at room temperature for this substrate. Purification by flash column chromatography (petrol /ethyl acetate, 4:1 to 3:1) afforded P23 as a white solid (235 mg, 0.50 mmol, 50%). mp 86-88 °C (CH2Cl2); Rf 0.63 (petrol/ethyl acetate, 3:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.26 (d, J = 8.9 Hz, 2H), 7.98 (d, J = 8.9 Hz, 2H), 7.98- 7.95 (m, 1H), 7.53 (td, J = 7.6, 1.3 Hz, 1H), 7.38 (t, J = 7.4 Hz, 1H), 7.29 (d, J = 7.6 Hz, 1H), 2.56 (s, 3H), 1.59 (d, J = 14.6 Hz, 1H), 1.50 (d, J = 14.6 Hz, 1H), 1.47 (s, 3H), 1.45 (s, 3H), 0.89 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 149.8, 148.1, 137.6, 137.3 (d, J = 19.5 Hz), 134.2, 133.0 (d, J = 1.8 Hz), 128.2 (d, J = 2.4 Hz), 128.1, 126.6, 124.0, 63.5 (d, J = 4.6 Hz), 56.5 (d, J = 3.0 Hz), 31.7, 31.5 (d, J = 3.1 Hz), 31.4, 31.1 (d, J = 6.6 Hz), 20.1 (d, J = 2.3 Hz); 19F NMR (377 MHz, CDCl ₃ ): δ (ppm) = 81.2 (s); IR (ATR): ṽ (cm ^–1 ) = 1531, 1349, 1327, 1306, 1164, 1147, 1086, 1059, 686, 620; HRMS (ESI ⁺ ) calcd. for C ₂₁ H ₂₈ FN ₃ O ₄ S ₂ Na ⁺ [M+Na] ⁺ : 492.1397, found: 492.1389. [00371] 3,5-Difluorophenyl-N-((4-nitrophenyl)sulfonyl)-N-(2,4,4-trim ethylpentan- 2-yl)benzenesulfondiimidoyl fluoride (P24) Prepared according to General Procedure B using P9 (710 mg, 1.50 mmol, 1.00 equiv.), THF (3.00 mL), NaH (64.0 mg, 60 % dispersion in mineral oil, 1.65 mmol, 1.10 equiv.) and NFSI (709 mg, 2.25 mmol, 1.50 equiv.). The N to S fluoride migration took 24 h at room temperature for this substrate. Purification by flash column chromatography (petrol /ethyl acetate, 4:1) afforded P24 as a white solid (373 mg, 0.76 mmol, 51%). mp 50-52 °C (CH ₂ Cl ₂ ); Rf 0.70 (petrol/ethyl acetate, 4:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.34 (d, J = 8.9 Hz, 2H), 8.08 (d, J = 8.9 Hz, 2H), 7.54 (ddd, J = 5.3, 2.3, 1.0 Hz, 2H), 7.13 (tt, J = 8.2, 2.3 Hz, 1H), 1.68 (d, J = 14.7 Hz, 1H), 1.54 (d, J = 14.7 Hz, 1H), 1.49 (s, 3H), 1.45 (s, 3H), 0.97 (s, 9H);13C NMR (101 MHz, CDCl3): δ (ppm) = 162.6 (dd, J = 256.0, 11.8 Hz), 150.1, 147.9, 141.2 (dt, J = 28.4, 9.6 Hz), 128.1, 124.3, 111.7-111.3 (second-order multiplet), 110.2 (t, J = 24.9 Hz), 64.0 (d, J = 4.6 Hz), 56.3 (d, J = 3.4 Hz), 31.82, 31.80, 31.46 (d, J = 6.1 Hz), 31.45; 19F NMR (377 MHz, CDCl3): δ (ppm) = 87.12 (s), -103.8- -103.9 (second-order multiplet); The second-order multiplet in the ¹³ C and ¹⁹ F NMR spectra arise due to virtual coupling; IR (ATR): ṽ (cm ^–1 ) = 1604, 1533, 1349, 1299, 1166, 1131, 1106, 1086; HRMS (ESI ⁺ ) calcd. for C20H24F3N3O4S2Na ⁺ [M+Na] ⁺ : 514.1053, found: 514.1053. [00372] 6-Methoxy-N-(4-nitrophenyl)sulfonyl)-N-(2,4,4-trimethylpenta n-2- yl)pyridine-3-sulfondiimidoyl fluoride (P25) Prepared according to General Procedure B using P10 (468 mg, 1.00 mmol, 1.00 equiv.), THF (2.00 mL), NaH (44.0 mg, 60 % dispersion in mineral oil, 1.10 mmol, 1.10 equiv.) and NFSI (473 mg, 1.50 mmol, 1.50 equiv.). The N to S fluoride migration took 24 h at room temperature for this substrate. Purification by flash column chromatography (petrol /ethyl acetate, 4:1 to 3:1) afforded P25 as a white solid (291 mg, 0.60 mmol, 60%). mp 70-72 °C (CH2Cl2); Rf 0.50 (petrol/ethyl acetate, 4:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.69 (d, J = 2.7 Hz, 1H), 8.29 (d, J = 9.0 Hz, 2H), 8.08- 8.05 (m, 1H), 8.04 (d, J = 9.0 Hz, 2H), 6.81 (dd, J = 9.0, 0.6 Hz, 1H), 3.98 (s, 3H), 1.65 (d, J = 14.7 Hz, 1H), 1.50 (d, J = 14.7 Hz, 1H), 1.47 (s, 3H), 1.42 (s, 3H), 0.95 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 167.2, 149.9, 148.2, 148.1, 137.3, 128.1, 127.7 (d, J = 24.8 Hz), 124.1, 111.6, 63.4 (d, J = 4.4 Hz), 56.4 (d, J = 3.1 Hz), 54.8, 31.8, 31.7 (d, J = 2.6 Hz), 31.5, 31.4 (d, J = 6.3 Hz); 19F NMR (377 MHz, CDCl3): δ (ppm) = 88.7 (s); IR (ATR): ṽ (cm ^–1 ) = 2980, 1588, 1532, 1484, 1381, 1348, 1310, 1288, 1163, 1086, 607; HRMS (ESI ⁺ ) calcd. for C20H27FN4O5S2Na ⁺ [M+Na] ⁺ : 509.1299, found: 509.1307. [00373] N-((4-Nitrophenyl)sulfonyl)-N-(2,4,4-trimethylpentan-2-yl)py ridine-3- sulfondiimidoyl fluoride (P26) Prepared according to General Procedure B using P11 (657 mg, 1.50 mmol, 1.00 equiv.), THF (3.00 mL), NaH (66.0 mg, 60 % dispersion in mineral oil, 1.65 mmol, 1.10 equiv.) and NFSI (709 mg, 2.25 mmol, 1.50 equiv.). The N to S fluoride migration took 72 h at room temperature for this substrate. Purification by flash column chromatography (CH ₂ Cl ₂ /ethyl acetate, 25:1 to 10:1) afforded P26 as a colourless oil (275 mg, 0.60 mmol, 40%). R _f 0.58 (CH ₂ Cl ₂ /ethyl acetate, 20:1); 1H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 9.10 (dd, J = 2.5, 0.8 Hz, 1H), 8.84 (dd, J = 4.9, 1.5 Hz, 1H), 8.31-8.27 (m,1 H), 8.29 (d, J = 9.0 Hz, 2H), 8.03 (d, J = 9.0 Hz, 2H), 7.50 (ddd, J = 8.3, 4.9, 0.8 Hz, 1H), 1.66 (d, J = 14.7 Hz, 1H), 1.52 (d, J = 14.7 Hz, 1H), 1.48 (s, 3H), 1.43 (s, 3H), 0.94 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 154.5, 150.0, 148.1, 147.9, 135.5 (d, J = 24.9 Hz), 135.1, 128.0, 124.2, 123.8, 63.8 (d, J = 4.5 Hz), 56.3 (d, J = 3.2 Hz), 31.8, 31.7, 31.44, 31.39; 19F NMR (377 MHz, CDCl3): δ (ppm) = 88.1 (s); IR (ATR): ṽ (cm ^–1 ) = 2981, 1532, 1473, 1462, 1382, 1251, 1162, 1085, 954; HRMS (ESI ⁺ ) calcd. for C19H25FN4O4S2Na ⁺ [M+Na] ⁺ : 479.1193, found: 479.1195. [00374] N-((4-Nitrophenyl)sulfonyl)-N-(2,4,4-trimethylpentan-2- yl)cyclopropanesulfondiimidoyl fluoride (P27) Prepared according to General Procedure B using P12 (401 mg, 1.00 mmol, 1.00 equiv.), THF (2.00 mL), NaH (44.0 mg, 60 % dispersion in mineral oil, 1.10 mmol, 1.10 equiv.) and NFSI (473 mg, 1.50 mmol, 1.50 equiv.). The N to S fluoride migration took 8 days at room temperature for this substrate. Purification by flash column chromatography (petrol/ethyl acetate, 4:1 to 3:1) afforded P27 as a colorless oil (390 mg, 0.93 mmol, 93%). Rf 0.63 (petrol/ethyl acetate, 3:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.34 (d, J = 8.9 Hz, 2H), 8.14 (d, J = 8.9 Hz, 2H), 3.50 (tq, J = 8.3, 4.3 Hz, 1H), 1.55-1.47 (m, 1H), 1.51 (d, J = 14.7 Hz, 1H), 1.43-1.36 (m, 1H), 1.39 (d, J = 14.7 Hz, 1H), 1.32 (s, 3H), 1.30-1.18 (m, 2H), 1.27 (s, 3H), 0.93 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 150.0, 148.7, 128.1, 124.2, 62.2 (d, J = 4.5 Hz), 56.5 (d, J = 2.5 Hz), 34.9 (d, J = 28.5 Hz), 31.7, 31.5, 31.4 (d, J = 2.7 Hz), 31.2 (d, J = 6.9 Hz), 8.2, 7.9 (d, J = 2.0 Hz); 19F NMR (377 MHz, CDCl3): δ (ppm) = 86.0 (s); IR (ATR): ṽ (cm ^–1 ) = 1531, 1349, 1334, 1299, 1160, 1071, 735, 686, 615; HRMS (ESI ⁺ ) calcd. for C ₁₇ H ₂₆ FN ₃ O ₄ S ₂ Na ⁺ [M+Na] ⁺ : 442.1241, found: 442.1241. [00375] N-((4-Nitrophenyl)sulfonyl)-N-(2,4,4-trimethylpentan-2- yl)ethanesulfondiimidoyl fluoride (P28) Prepared according to General Procedure B using P13 (389 mg, 1.00 mmol, 1.00 equiv.), THF (2.00 mL), NaH (44.0 mg, 60 % dispersion in mineral oil, 1.10 mmol, 1.10 equiv.) and NFSI (473 mg, 1.50 mmol, 1.50 equiv.). The N to S fluoride migration took 12 h at room temperature for this substrate. Purification by flash column chromatography (petrol/ethyl acetate, 4:1) afforded P28 as a white solid (286 mg, 0.70 mmol, 70%). mp 80-82 °C (CH ₂ Cl ₂ ); R _f 0.52 (petrol/ethyl acetate, 4:1); 1H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.30 (d, J = 9.0 Hz, 2H), 8.08 (d, J = 9.0 Hz, 2H), 3.90- 3.69 (m, 2H), 1.53-1.47 (m, 4H), 1.36 (d, J = 14.7 Hz, 1H), 1.31 (s, 3H), 1.23 (s, 3H), 0.90 (s, 9H); 13C NMR (101 MHz, CDCl3): 149.8, 148.4, 128.0, 124.1, 62.1 (d, J = 4.7 Hz), 56.2 (d, J = 2.7 Hz), 52.5 (d, J = 17.0 Hz), 31.7, 31.39 (d, J = 2.7 Hz), 31.36, 31.1 (d, J = 6.8 Hz), 8.7 (note: for the gem-dimethyl carbons in the tert-octyl group, NC(CH3)2CH2C(CH3)3, 2 peaks were found instead of 1 due to the loss of symmetry caused by chiral sulfur atom); 19F NMR (377 MHz, CDCl3): δ (ppm) = 77.9 (s); IR (ATR): ṽ (cm ^–1 ) = 1531, 1349, 1161, 1081, 1056, 739; HRMS (ESI ⁺ ) calcd. for C16H26FN3O4S2Na ⁺ [M+Na] ⁺ : 430.1241, found: 430.1240. [00376] N-((4-Nitrophenyl)sulfonyl)-N-(2,4,4-trimethylpentan-2- yl)ethenesulfondiimidoyl fluoride (P29) Prepared according to General Procedure B using P14 (418 mg, 1.08 mmol, 1.00 equiv.), THF (3.60 mL), NaH (48.0 mg, 60 % dispersion in mineral oil, 1.20 mmol, 1.10 equiv.) and NFSI (510 mg, 1.62 mmol, 1.50 equiv.). The N to S fluoride migration took 24 h at room temperature for this substrate. Purification by flash column chromatography (petrol/ethyl acetate, 3:1) afforded P29 as a colourless oil (210 mg, 0.52 mmol, 48%). R _f 0.62 (petrol/ethyl acetate, 3:1); 1H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.33 (d, J = 8.8 Hz, 2H), 8.11 (d, J = 8.8 Hz, 2H), 7.04 (ddd, J = 16.0, 9.6, 2.3 Hz, 1H), 6.55 (dd, J = 16.0, 1.5 Hz, 1H), 6.25 (ddd, J = 9.6, 4.5, 1.5 Hz, 1H), 1.59 (d, J = 14.7 Hz, 1H), 1.43 (d, J = 14.7 Hz, 1H), 1.37 (s, 3H), 1.32 (s, 3H), 0.93 (s, 9H); 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 149.9, 148.3, 134.1 (d, J = 29.0 Hz), 130.3, 128.1, 124.2, 62.6 (d, J = 4.6 Hz), 56.2 (d, J = 3.1 Hz), 31.7, 31.6 (d, J = 2.7 Hz), 31.5 (d, J = 6.3 Hz), 31.4; 19F NMR (377 MHz, CDCl ₃ ): δ (ppm) = 86.5 (s); IR (ATR): ṽ (cm ^–1 ) = 1531, 1348, 1312, 1161, 1082, 741, 616; HRMS (ESI ⁺ ) calcd. for C ₁₆ H ₂₄ FN ₃ O ₄ S ₂ Na ⁺ [M+Na] ⁺ : 428.1084, found: 428.1084. [00377] 3-Cyano-4-ethoxy-N-((4-nitrophenyl)sulfonyl)-N-(2,4,4-trimet hylpentan-2- yl)benzenesulfondiimidoyl fluoride (P30) Prepared according to General Procedure B using P15 (3.84 g, 7.58 mmol, 1.00 equiv.), THF (15.2 mL), NaH (334 mg, 60 % dispersion in mineral oil, 8.35 mmol, 1.10 equiv.) and NFSI (3.58 g, 11.37 mmol, 1.50 equiv.). The N to S fluoride migration took 20 h at room temperature for this substrate. Purification by flash column chromatography (petrol/ethyl acetate, 2:1) afforded P30 as a white solid (1.91 g, 3.65 mmol, 48%). mp 120-122 °C (CH2Cl2); Rf 0.58 (petrol /ethyl acetate, 2:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.32 (d, J = 8.9 Hz, 2H), 8.15 (dd, J = 9.1, 2.6 Hz, 1H), 8.11 (d, J = 2.6 Hz, 1H), 8.06 (d, J = 8.9 Hz, 2H), 7.09 (d, J = 9.1 Hz, 1H), 4.26 (q, J = 7.0 Hz, 2H), 1.66 (d, J = 14.7 Hz, 1H), 1.54-1.49 (m, 4H), 1.46 (s, 3H), 1.42 (s, 3H), 0.95 (s, 9H); 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 164.4, 150.0, 148.0, 133.83, 133.81, 130.2 (d, J = 26.9 Hz), 128.1, 124.2, 114.2, 112.7, 103.4, 66.3, 63.6 (d, J = 4.3 Hz), 56.3 (d, J = 3.1 Hz), 31.8, 31.7 (d, J = 2.8 Hz), 31.43, 31.37 (d, J = 6.2 Hz), 14.3; 19F NMR (377 MHz, CDCl ₃ ): δ (ppm) = 87.8 (s); IR (ATR): ṽ (cm ^–1 ) = 2981, 1527, 1473, 1383, 1251, 1151, 1072, 955, 615; HRMS (ESI ⁺ ) calcd. for C ₂₃ H ₂₉ FN ₄ O ₅ S ₂ Na ⁺ [M+Na] ⁺ : 547.1456, found: 547.1456. [00378] 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-N-((4- nitrophenyl)sulfonyl)-N-(2,4,4-trimethylpentan-2-yl)benzenes ulfondiimidoyl fluoride (P31) Prepared according to General Procedure B using P16 (661 mg, 1.00 mmol, 1.00 equiv.), THF (2.00 mL), NaH (44.0 mg, 60 % dispersion in mineral oil, 1.10 mmol, 1.10 equiv.) and NFSI (473 mg, 1.50 mmol, 1.50 equiv.). The N to S fluoride migration took 24 h at room temperature for this substrate. Purification by flash column chromatography (petrol/ethyl acetate, 4:1 to 3:1) afforded P31 as a colourless oil (350 mg, 0.52 mmol, 52%). Rf 0.64 (petrol/ethyl acetate, 3:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.30 (d, J = 8.9 Hz, 2H), 8.06 (d, J = 8.9 Hz, 2H), 7.98 (d, J = 8.9 Hz, 2H), 7.53 (d, J = 8.9 Hz, 2H), 7.21 (d, J = 8.0 Hz, 2H), 7.14 (d, J = 8.0 Hz, 2H), 6.75 (s, 1H), 2.40 (s, 3H), 1.67 (d, J = 14.7 Hz, 1H), 1.53 (d, J = 14.7 Hz, 1H), 1.48 (s, 3H), 1.43 (s, 3H), 0.96 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 149.9, 148.1, 145.5, 144.5 (q, J = 38.8 Hz), 143.8, 140.2, 137.3 (d, J = 25.1 Hz), 130.0, 128.8, 128.6, 128.1, 125.6, 125.2, 124.2, 121.0 (q, J = 269.2 Hz), 106.9, 63.5 (d, J = 4.2 Hz), 56.3 (d, J = 2.7 Hz), 31.78 (d, J = 2.2 Hz), 31.76, 31.43, 31.35 (d, J = 5.9 Hz), 21.4; 19F NMR (377 MHz, CDCl ₃ ): δ (ppm) = 86.7 (s), -62.5 (s); IR (ATR): ṽ (cm ^–1 ) = 1530, 1348, 1237, 1161, 1135, 1107, 974, 744; HRMS (ESI ⁺ ) calcd. for C ₃₁ H ₃₃ F ₄ N ₅ O ₄ S ₂ Na ⁺ [M+Na] ⁺ : 702.1802, found: 702.1799. [00379] Preparation of TIPS-NH ₂ (TIPS = iPr ₃ Si) (P32) [00380] Triisopropylsilyl chloride (13.50 g, 70.0 mmol, 1.00 equiv.) was dissolved in anhydrous diethyl ether (140 mL) in an oven-dried 500 mL round-bottom flask. The reaction mixture was cooled to -78 °C. Anhydrous ammonia was bubbled through this solution for 2 h, resulting in the immediate formation of a white precipitate. The reaction was then warmed to 0 °C and stirred for another 3 h to remove excess ammonia. Filtration over anhydrous Na ₂ SO ₄ and removal of solvent under reduced pressure afforded TIPS-NH ₂ as a colourless oil (12.0 g, 69.5 mmol, 99%). 1H NMR (400 MHz, C6D6): δ (ppm) = 1.05-1.00 (m, 18H), 0.95-0.85 (m, 3H), -0.12 (s, 2H); 13C NMR (101MHz, C ₆ D ₆ ): δ (ppm) = 18.4, 12.5; IR (ATR): ṽ (cm ^–1 ) = 2864, 1546, 1463, 1382, 1245, 1011, 882, 817, 658; [00381] Preparation of Sulfinylamine (P33) [00382] TIPS-NH2 (5.20 g, 30.0 mmol, 1.00 equiv.) was dissolved in anhydrous diethyl ether (600 mL) in an oven-dried 1 L round-bottom flask. The reaction was cooled to 0 °C and anhydrous Et3N (8.41 mL, 61.8 mmol, 2.06 equiv.) was added. Freshly distilled thionyl chloride (2.25 mL, 30.9 mmol, 1.03 equiv.) was then added dropwise. The reaction was stirred at 0 °C for 1.5 h. Filtration over Na2SO4 (washed with diethyl ether) and removal of solvent under reduced pressure at room temperature afforded TIPS-NSO as a pale-yellow oil (6.56 g, 30.0 mmol, 100%). 1H NMR (400 MHz, C6D6): δ (ppm) = 1.19-0.96 (m, 21H); 13C NMR (101MHz, C6D6): δ (ppm) = 18.0, 12.4; IR (ATR): ṽ (cm ^–1 ) = 2980, 1463, 1385, 1308, 1128, 882, 682, 664. [00383] N-(S-(4-Fluorophenyl)-N-(triisopropylsilyl)sulfinimidoyl)-4- nitrobenzenesulfonamide (P34) [00384] TIPS-NSO P33 (1.73 g, 7.90 mmol, 1.00 equiv.) was dissolved in anhydrous THF (15.8 mL) in an oven-dried 250 mL round-bottom flask and was purged with nitrogen gas. The mixture was cooled to -30 °C before LiHMDS (7.90 mL, 1.0 M in THF, 7.90 mmol, 1.00 equiv.) was added. After being stirred at - 30 °C for 5 min, the reaction was warmed to 0 °C and stirred for another 10 min. TMSCl (1.00 mL, 7.90 mmol, 1.00 equiv.) was added and the reaction was stirred at 0 °C for 10 min.4-Fluorophenylmagnesium bromide solution (10.53 mL, 0.90 M in THF, 9.48 mmol, 1.20 equiv.) was then added and the reaction was stirred at 0 °C for 10 min. The reaction mixture was then quenched with sat. aq. tetrasodium EDTA solution (250 mL). Ethyl acetate (150 mL) was added and the organic layer was separated. The aqueous layer was further extracted with ethyl acetate (2 × 80 mL). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The crude mixture was dissolved in anhydrous CH ₂ Cl ₂ (39.5 mL) in an oven-dried 250 mL round-bottom flask before Et ₃ N (1.32 mL, 9.48 mmol, 1.20 equiv.) and NsCl (1.75 g, 7.90 mmol, 1.00 equiv.) were added. The reaction was stirred at 0 °C for 20 min and then was quenched with sat. aq. NaCl solution and extracted with CH2Cl2 (3 × 100 mL). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered, concentrated under reduced pressure and purified by flash column chromatography (CH2Cl2/ethyl acetate, 100:1 to 30:1 to 20:1) to afford sulfinamidine P34 as a white solid (3.52 g, 7.05 mmol, 89%). mp 148-150 °C (CH2Cl2); Rf 0.64 (CH2Cl2/ethyl acetate, 25:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.18 (d, J = 8.9 Hz, 2H), 7.87 (d, J = 8.9 Hz, 2H), 7.63- 7.58 (m, 2H), 7.13-7.07 (m, 2H), 4.53 (s, 1H), 1.32-1.20 (m, 3H), 1.13-1.06 (m, 18H);13C NMR (101 MHz, CDCl3): δ (ppm) = 164.7 (d, J = 254.8 Hz), 150.3, 149.2, 136.6 (d, J = 3.2 Hz), 128.8 (d, J = 9.1 Hz), 127.4, 123.8, 116.8 (d, J = 22.7 Hz), 17.94, 17.90, 12.0 (note: for dimethyl carbons in triisopropylsilyl group, NSi (CH(CH3)2 )3; 19F NMR (377 MHz, CDCl ₃ ): δ (ppm) = -106.7 (tt, J = 8.1, 4.9 Hz); IR (ATR): ṽ (cm ^–1 ) = 1527, 1490, 1389, 1347, 1299, 1227, 1149, 1088, 954,786, 608; HRMS (ESI ⁺ ) calcd. for C ₂₁ H ₃₁ FN ₃ O ₄ S ₂ Si ⁺ [M+H] ⁺ : 500.1504, found: 500.1504. [00385] 4-Fluoro-N-((4-nitrophenyl)sulfonyl)-N-(triisopropylsilyl)be nzene- sulfondiimidoyl fluoride (P35) [00386] Prepared according to General Procedure B using P34 (998 mg, 2.00 mmol, 1.00 equiv.), THF (4.00 mL), NaH (88 mg, 60 % dispersion in mineral oil, 2.20 mmol, 1.10 equiv.) and NFSI (945 mg, 3.00 mmol, 1.50 equiv.). Purification by flash column chromatography (petrol/ethyl acetate, 6:1) afforded P35 as a colourless oil (941 mg, 1.82 mmol, 91%). Rf 0.42 (petrol/ethyl acetate, 6:1); 1H NMR (400 MHz, CD3CN): δ (ppm) = 8.27 (d, J = 9.0 Hz, 2H), 8.00-7.94 (m, 4H), 7.34-7.28 (m, 2H), 1.23-1.13 (m, 3H), 1.05 (d, J = 2.9 Hz, 9H), 1.03 (d, J = 2.9 Hz, 9H); 13C NMR (101 MHz, CD3CN): δ (ppm) = 167.0 (d, J = 256.4 Hz), 151.1, 148.8, 136.2 (dd, J = 28.5, 3.1 Hz), 131.3 (d, J = 10.2 Hz), 128.8, 125.3, 118.0 (d, J = 23.5 Hz), 18.3, 18.2, 13.4 (d, J = 1.9 Hz); 19F NMR (377 MHz, CD3CN): δ (ppm) = 87.6, -103.3 (tt, J = 8.7, 4.8 Hz); IR (ATR): ṽ (cm ^–1 ) = 1531, 1403, 1348, 1251, 1163, 1113, 1090, 855, 683, 614; HRMS (ESI ⁺ ) calcd. for C21H29F2N3O4S2SiNa ⁺ [M+Na] ⁺ : 540.1229, found: 540.1228. [00387] General Procedure C - Sulfondiimidamide Synthesis Sulfondiimidoyl fluoride (1.00 equiv.), Ca(NTf ₂ ) ₂ (1.10 equiv.) and amine (2.20-6.00 equiv.) were added to an oven-dried round-bottom flask and dissolved in anhydrous t-Amyl-OH (0.5 M). The reaction was stirred at 60-80 °C until completion was observed by TLC (12-36 h). The mixture was then diluted with CH2Cl2 and quenched with sat. aq. NaCl solution. The organic layers were separated and the aqueous layers was further extracted with CH2Cl2 ×2. The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by flash column chromatography to afford the sulfondiimidamide product. Note: Emulsification may form during extraction on a large reaction scale. In this case, 0.5 M aq. HCl solution can be used to do the workup instead of sat. aq. NaCl solution to facilitate easier separation. [00388] N-((4-Fluorophenyl)(morpholino)((triisopropylsilyl)imino)-l6 - sulfaneylidene)-4-nitrobenzenesulfonamide (P36) [00389] Prepared according to General Procedure C using sulfondiimidoyl fluoride P35 (305 mg, 0.59 mmol, 1.00 equiv.), Ca(NTf ₂ ) ₂ (389 mg, 0.65 mmol, 1.10 equiv.), morpholine (113 mg, 1.30 mmol, 2.20 equiv.) and t-AmylOH (1.18 mL). The reaction was stirred at 60 °C for 45 h. The aqueous layers was extracted with ethyl acetate (instead of CH ₂ Cl ₂ ). Purification by flash column chromatography (petrol/ethyl acetate, 3:1 to 2:1) afforded sulfondiimidamide P36 as a colourless oil (252 mg, 0.43 mmol, 73%). R _f 0.41 (petrol/ethyl acetate, 3:1); 1H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.26 (d, J = 8.9 Hz, 2H), 8.04 (d, J = 8.9 Hz, 2H), 7.87- 7.82 (m, 2H), 7.18-7.12 (m, 2H), 3.68 (td, J = 4.3, 2.0 Hz, 4H), 3.15 (dt, J = 11.8, 4.6 Hz, 2H), 3.03 (dt, J = 11.8, 4.6 Hz, 2H), 1.07-0.96 (m, 21H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 165.2 (d, J = 256.3 Hz), 149.8, 149.4, 135.8 (d, J = 3.2 Hz), 130.2 (d, J = 9.2 Hz), 127.6, 123.8, 116.3 (d, J = 22.6 Hz), 66.3, 46.5, 18.3, 13.2; 19F NMR (377 MHz, CDCl3): δ (ppm) = -104.7 (tt, J = 8.0, 5.0 Hz); IR (ATR): ṽ (cm ^–1 ) = 1529, 1374, 1297, 1153, 1086, 1064, 1011, 922, 738, 680; HRMS (ESI ⁺ ) calcd. for C25H37FN4O5S2SiNa ⁺ [M+Na] ⁺ : 607.1851, found: 607.1849. [00390] N-((4-Fluorophenyl)(morpholino)((2,4,4-trimethylpentan-2-yl) imino)-λ6- sulfaneylidene)-4-nitrobenzenesulfonamide (E1) Sulfondiimidoyl fluoride P17 (120 mg, 0.25 mmol, 1.00 equiv.), Ca(NTf ₂ ) ₂ (167 mg, 0.278 mmol, 1.10 equiv.) and morpholine (48 mg, 0.55 mmol, 2.20 equiv.) were added to an oven- dried 10 mL round-bottom flask and dissolved in anhydrous t-AmylOH (0.5 mL). The reaction was stirred at 60 °C for 24 h until completion was observed by TLC. The mixture was then diluted with CH ₂ Cl ₂ (30 mL) and quenched with sat. aq. NaCl solution (50 mL). The organic layers were separated and the aqueous layers was further extracted with CH ₂ Cl ₂ (2 × 20 mL). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The crude product was purified by flash column chromatography (petrol/ethyl acetate, 3:1 to 1:1) to afford sulfondiimidamide E1 as a white solid (126 mg, 0.23 mmol, 93%). mp 55-57 °C (CH2Cl2); Rf 0.50 (petrol/ethyl acetate, 2:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.19 (d, J = 8.8 Hz, 2H), 7.84 (d, J = 8.8 Hz, 2H), 7.71 -7.64 (m, 2H), 7.09-7.02 (m, 2H), 3.68 (t, J = 4.5 Hz, 4H), 3.11 (dt, J = 12.0, 4.5 Hz, 2H), 3.04 (dt, J = 12.0, 4.5 Hz, 2H), 1.71 (d, J = 14.5 Hz, 1H), 1.59-1.51 (m, 4H), 1.48 (s, 3H), 1.05 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 165.1 (d, J = 256.1 Hz), 149.5, 149.3, 133.5 (d, J = 3.1 Hz), 130.7 (d, J = 9.2 Hz), 127.5, 123.8, 116.1 (d, J = 22.7 Hz), 66.6, 60.3, 57.6, 47.0, 32.1, 31.92, 31.87, 31.5; 19F NMR (377 MHz, CDCl3): δ (ppm) = -105.1 (tt, J = 7.9, 4.9 Hz); IR (ATR): ṽ (cm ^–1 ) = 2362, 1529, 1350, 1298, 1154, 1088, 1050, 921; HRMS (ESI ⁺ ) calcd. for C24H33FN4O5S2Na ⁺ [M+Na] ⁺ : 563.1769, found: 563.1766. [00391] N-((4-Chlorophenyl)(morpholino)((2,4,4-trimethylpentan-2-yl) imino)-λ6- sulfaneylidene)-4-nitrobenzenesulfonamide (E2) Prepared according to General Procedure C using sulfondiimidoyl fluoride P18 (88 mg, 0.18 mmol, 1.00 equiv.), Ca(NTf ₂ ) ₂ (119 mg, 0.198 mmol, 1.10 equiv.), morpholine (35 mg, 0.40 mmol, 2.20 equiv.) and t-AmylOH (0.36 mL). The reaction was stirred at 60 °C for 24 h. Purification by flash column chromatography (petrol/ethyl acetate, 4:1 to 3:2) afforded sulfondiimidamide E2 as a white solid (95 mg, 0.17 mmol, 94%). mp 128-130 °C (CH ₂ Cl ₂ ); Rf 0.61 (petrol/ethyl acetate, 2:1); 1H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.19 (d, J = 8.9 Hz, 2H), 7.84 (d, J = 8.9 Hz, 2H), 7.59 (d, J = 8.8 Hz, 2H), 7.34 (d, J = 8.8 Hz, 2H), 3.68 (ddd, J = 5.2, 3.8, 1.2 Hz, 4H), 3.11 (dt, J = 12.0, 4.5 Hz, 2H), 3.04 (dt, J = 12.0, 4.5 Hz, 2H), 1.71 (d, J = 14.5 Hz, 1H), 1.55 (s, 3H), 1.55 (d, J = 14.5 Hz, 1H), 1.48 (s, 3H), 1.05 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 149.4, 149.3, 139.4, 136.1, 129.4, 129.2, 127.5, 123.8, 66.6, 60.3, 57.5, 47.0, 32.1, 31.92, 31.86, 31.5; IR (ATR): ṽ (cm ^–1 ) = 1528, 1349, 1299, 1257, 1153, 1087, 1062, 1009, 919, 746; HRMS (ESI ⁺ ) calcd. for C24H33ClN4O5S2Na ⁺ [M+Na] ⁺ : 579.1473, found: 579.1475. [00392] N-((3-Chlorophenyl)(morpholino)((2,4,4-trimethylpentan-2-yl) imino)-λ6- sulfaneylidene)-4-nitrobenzenesulfonamide (E3) Prepared according to General Procedure C using sulfondiimidoyl fluoride P19 (160 mg, 0.33 mmol, 1.00 equiv.), Ca(NTf2)2 (216 mg, 0.36 mmol, 1.10 equiv.), morpholine (63 mg, 0.72 mmol, 2.20 equiv.) and t-AmylOH (0.65 mL). The reaction was stirred at 60 °C for 24 h. Purification by flash column chromatography (petrol/ethyl acetate, 3:1 to 1:1) afforded sulfondiimidamide E3 as a white solid (162 mg, 0.29 mmol, 89%). mp 112-114 °C (CH2Cl2); Rf 0.73 (petrol/ethyl acetate, 1:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.16 (d, J = 8.8 Hz, 2H), 7.78 (d, J = 8.8 Hz, 2H), 7.54 (ddd, J = 8.0, 2.0, 1.0 Hz, 1H), 7.43 (ddd, J = 8.0, 2.0, 1.0 Hz, 1H), 7.39 (t, J = 2.0 Hz, 1H), 7.31 (t, J = 8.0 Hz, 1H), 3.67 (ddd, J = 5.6, 3.8, 1.8 Hz, 4H), 3.10 (dt, J = 12.0, 4.2 Hz, 2H), 3.03 (dt, J = 12.0, 4.2 Hz, 2H), 1.75 (d, J = 14.5 Hz, 1H), 1.61 (s, 3H), 1.57 (d, J = 14.5 Hz, 1H), 1.50 (s, 3H), 1.06 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 149.3, 149.1, 139.0, 135.0, 132.6, 130.2, 127.6, 127.4, 126.3, 123.8, 66.5, 60.5, 57.4, 46.9, 32.0, 31.9, 31.8, 31.5; IR (ATR): ṽ (cm ^–1 ) = 1528, 1349, 1296, 1255, 1153, 1112, 1088, 1049, 917, 733, 677; HRMS (ESI ⁺ ) calcd. for C ₂₄ H ₃₃ ClN ₄ O ₅ S ₂ Na ⁺ [M+Na] ⁺ : 579.1473, found: 579.1469. [00393] N-((4-Cyanophenyl)(morpholino)((2,4,4-trimethylpentan-2-yl)i mino)-λ6- sulfaneylidene)-4-nitrobenzenesulfonamide (E4) Prepared according to General Procedure C using sulfondiimidoyl fluoride P20 (200 mg, 0.42 mmol, 1.00 equiv.), Ca(NTf ₂ ) ₂ (275 mg, 0.46 mmol, 1.10 equiv.), morpholine (80 mg, 0.92 mmol, 2.20 equiv.) and t-AmylOH (0.83 mL). The reaction was stirred at 60 °C for 12 h. Purification by flash column chromatography (petrol/ethyl acetate, 3:1 to 1:1) afforded sulfondiimidamide E4 as a white solid (213 mg, 0.39 mmol, 93%). mp 154-156 °C (CH ₂ Cl ₂ ); Rf 0.54 (petrol/ethyl acetate, 1:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.21 (d, J = 8.9 Hz, 2H), 7.87 (d, J = 8.9 Hz, 2H), 7.81 (d, J = 8.8 Hz, 2H), 7.71 (d, J = 8.8 Hz, 2H), 3.66 (t, J = 4.8 Hz, 4H), 3.09 (dt, J = 12.0, 4.6 Hz, 2H), 3.01 (dt, J = 12.0, 4.6 Hz, 2H), 1.69 (d, J = 14.5 Hz, 1H), 1.54 (d, J = 14.5 Hz, 1H), 1.52 (s, 3H), 1.46 (s, 3H), 1.02 (s, 9H); 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 149.4, 149.1, 142.2, 132.7, 128.5, 127.4, 123.9, 117.1, 116.2, 66.4, 60.5, 57.3, 46.9, 31.9, 31.79, 31.75, 31.4; IR (ATR): ṽ (cm ^–1 ) = 1528, 1349, 1299, 1257, 1154, 1086, 1045, 917, 733; HRMS (ESI ⁺ ) calcd. for C25H33N5O5S2Na ⁺ [M+Na] ⁺ : 570.1815, found: 570.1812. [00394] N-((3-Cyanophenyl)(morpholino)((2,4,4-trimethylpentan-2-yl)i mino)-λ6- sulfaneylidene)-4-nitrobenzenesulfonamide (E5) Prepared according to General Procedure C using sulfondiimidoyl fluoride P21 (285 mg, 0.59 mmol, 1.00 equiv.), Ca(NTf ₂ ) ₂ (392 mg, 0.46 mmol, 1.10 equiv.), morpholine (114 mg, 1.31 mmol, 2.20 equiv.) and t-AmylOH (1.19 mL). The reaction was stirred at 60 °C for 12 h. Purification by flash column chromatography (petrol/ethyl acetate, 2:1 to 1:1) afforded sulfondiimidamide E5 as a white solid (300 mg, 0.55 mmol, 92%). mp 160-162 °C (CH ₂ Cl ₂ ); Rf 0.60 (petrol/ethyl acetate, 1:1); 1H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.24 (d, J = 8.8 Hz, 2H), 7.93-7.85 (m, 2H), 7.87 (d, J = 8.8 Hz, 2H), 7.80 (dt, J = 7.8, 1.3 Hz, 1H), 7.56 (t, J = 7.8 Hz, 1H), 3.70 (ddd, J = 5.3, 3.8, 1.1 Hz, 4H), 3.12 (dt, J = 12.0, 4.6 Hz, 2H), 3.04 (dt, J = 12.0, 4.6 Hz, 2H), 1.74 (d, J = 14.7 Hz, 1H), 1.59 (d, J = 14.7 Hz, 1H), 1.58 (s, 3H), 1.50 (s, 3H), 1.06 (s, 9H); 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 149.6, 149.1, 139.4, 135.7, 131.73, 131.65, 130.1, 127.5, 124.1, 117.1, 113.7, 66.5, 60.8, 57.5, 47.1, 32.1, 31.91, 31.90, 31.5; IR (ATR): ṽ (cm ^–1 ) = 2980, 1529, 1385, 1350, 1298, 1257, 1154, 1088, 1064, 922; HRMS (ESI ⁺ ) calcd. for C ₂₅ H ₃₃ N ₅ O ₅ S ₂ Na ⁺ [M+Na] ⁺ : 570.1815, found: 570.1811. [00395] N-((4-Methoxyphenyl)(morpholino)((2,4,4-trimethylpentan-2-yl )imino)-λ6- sulfaneylidene)-4-nitrobenzenesulfonamide (E6) Prepared according to General Procedure C using sulfondiimidoyl fluoride P22 (110 mg, 0.23 mmol, 1.00 equiv.), Ca(NTf2)2 (150 mg, 0.25 mmol, 1.10 equiv.), morpholine (44 mg, 0.51 mmol, 2.20 equiv.) and t-AmylOH (0.45 mL). The reaction was stirred at 60 °C for 24 h. Purification by flash column chromatography (petrol/ethyl acetate, 3:1 to 1:1) afforded sulfondiimidamide E6 as a white solid (115 mg, 0.21 mmol, 92%). mp 132-134 °C (CH2Cl2); Rf 0.59 (petrol/ethyl acetate, 1:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.10 (d, J = 8.9 Hz, 2H), 7.77 (d, J = 8.9 Hz, 2H), 7.50 (d, J = 9.0 Hz, 2H), 6.75 (d, J = 9.0 Hz, 2H), 3.77 (s, 3H), 3.65 (ddd, J = 5.7, 3.6, 2.0 Hz, 4H), 3.10 (dt, J = 12.0, 4.1 Hz, 2H), 3.03 (dt, J = 12.0, 4.1 Hz, 2H), 1.70 (d, J = 14.5 Hz, 1H), 1.56 (s, 3H), 1.53 (d, J = 14.5 Hz, 1H), 1.47 (s, 3H), 1.04 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 162.9, 149.6, 149.1, 130.0, 128.5, 127.6, 123.6, 113.9, 66.6, 59.9, 57.6, 55.7, 46.8, 32.1, 31.9, 31.8, 31.5; IR (ATR): ṽ (cm ^–1 ) = 2981, 1530, 1383, 1348, 1296, 1254, 1151, 1087, 1063, 914, 733; HRMS (ESI ⁺ ) calcd. for C ₂₅ H ₃₇ N ₄ O ₆ S ₂ ⁺ [M+H] ⁺ : 553.2149, found: 553.2144. [00396] N-(Morpholino(o-tolyl)((2,4,4-trimethylpentan-2-yl)imino)-λ 6- sulfaneylidene)-4-nitrobenzenesulfonamide (E7) Prepared according to General Procedure C using sulfondiimidoyl fluoride P23 (175 mg, 0.37 mmol, 1.00 equiv.), Ca(NTf ₂ ) ₂ (244 mg, 0.41 mmol, 1.10 equiv.), morpholine (129 mg, 1.48 mmol, 4.00 equiv.) and t-AmylOH (0.75 mL). The reaction was stirred at 75 °C for 18 h. Purification by flash column chromatography (petrol/ethyl acetate, 3:1 to 2:1) afforded sulfondiimidamide E7 as a white solid (149 mg, 0.28 mmol, 75%). mp 114-116 °C (CH2Cl2); Rf 0.46 (petrol/ethyl acetate, 2:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.09 (d, J = 8.9 Hz, 2H), 8.08-8.05 (m, 1H), 7.71 (d, J = 8.9 Hz, 2H), 7.36 (td, J = 7.5, 1.4 Hz, 1H), 7.26-7.21 (m, 1H), 7.06 (dt, J = 7.5, 1.4 Hz, 1H), 3.65 (td, J = 5.8, 3.4 Hz, 4H), 3.29 (ddd, J = 12.3, 6.0, 4.0 Hz, 2H), 3.16 (ddd, J = 12.3, 6.0, 4.0 Hz, 2H), 2.30 (s, 3H), 1.72 (d, J = 14.5 Hz, 1H), 1.66 (d, J = 14.5 Hz, 1H), 1.51 (s, 3H), 1.49 (s, 3H), 1.04 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 149.12, 149.10, 138.0, 137.0, 133.6, 132.6, 131.8, 127.5, 126.4, 123.6, 66.4, 60.4, 57.7, 45.3, 32.1, 31.9, 31.8, 31.5, 21.2; IR (ATR): ṽ (cm ^–1 ) =2980, 1527, 1349, 1296, 1257, 1151, 1061, 1034, 919, 734; HRMS (ESI ⁺ ) calcd. for C25H36N4O5S2Na ⁺ [M+Na] ⁺ : 559.2019, found: 559.2010. [00397] N-((3,5-Difluorophenyl)(morpholino)((2,4,4-trimethylpentan-2 -yl)imino)- λ6-sulfaneylidene)-4-nitrobenzenesulfonamide (E8) Prepared according to General Procedure C using sulfondiimidoyl fluoride P24 (310 mg, 0.63 mmol, 1.00 equiv.), Ca(NTf ₂ ) ₂ (417 mg, 0.70 mmol, 1.10 equiv.), morpholine (121 mg, 1.39 mmol, 2.20 equiv.) and t-AmylOH (1.26 mL). The reaction was stirred at 60 °C for 36 h. Purification by flash column chromatography (petrol/ethyl acetate, 3:1 to 2:1) afforded sulfondiimidamide E8 as a white solid (328 mg, 0.59 mmol, 93%). mp 152-154 °C (CH2Cl2); Rf 0.37 (petrol/ethyl acetate, 3:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.23 (d, J = 8.8 Hz, 2H), 7.88 (d, J = 8.8 Hz, 2H), 7.16- 7.13 (m, 2H), 6.96 (tt, J = 8.2, 2.3 Hz, 1H), 3.69 (t, J = 4.7 Hz, 4H), 3.11 (dt, J = 12.0, 4.6 Hz, 2H), 3.04 (dt, J = 12.0, 4.6 Hz, 2H), 1.75 (d, J = 14.5 Hz, 1H), 1.58 (d, J = 14.5 Hz, 1H), 1.58 (s, 3H), 1.49 (s, 3H), 1.06 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 162.6 (dd, J = 254.9, 11.7 Hz), 149.5, 149.1, 141.2 (t, J = 8.2 Hz), 127.5, 124.0, 111.6-111.3 (second-order multiplet), 108.3 (t, J = 25.1 Hz), 66.5, 60.8, 57.5, 47.0, 32.0, 31.90, 31.86, 31.5; 19F NMR (377 MHz, CDCl3): δ (ppm) = -105.22- -105.24 (second-order multiplet); IR (ATR): ṽ (cm ^–1 ) = 2980, 1601, 1529, 1350, 1293, 1257, 1157, 1090, 1066, 920; HRMS (ESI ⁺ ) calcd. for C24H32F2N4O5S2Na ⁺ [M+Na] ⁺ : 581.1674, found: 581.1664. [00398] N-((6-Methoxypyridin-3-yl)(morpholino)((2,4,4-trimethylpenta n-2- yl)imino)-λ6-sulfaneylidene)-4-nitrobenzenesulfonamide (E9) Prepared according to General Procedure C using sulfondiimidoyl fluoride P25 (290 mg, 0.60 mmol, 1.00 equiv.), Ca(NTf ₂ ) ₂ (394 mg, 0.66 mmol, 1.10 equiv.), morpholine (115 mg, 1.32 mmol, 2.20 equiv.) and t-AmylOH (1.20 mL). The reaction was stirred at 60 °C for 36 h. Purification by flash column chromatography (petrol /ethyl acetate, 3:1 to 1:1) afforded sulfondiimidamide E9 as a white solid (307 mg, 0.56 mmol, 93%). mp 140-142 °C (CH2Cl2); Rf 0.44 (petrol/ethyl acetate, 2:1); 1H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.29 (d, J = 2.6 Hz, 1H), 8.14 (d, J = 8.8 Hz, 2H), 7.80 (d, J = 8.8 Hz, 2H), 7.77 (dd, J = 8.9, 2.6 Hz, 1H), 6.65 (d, J = 8.9 Hz, 1H), 3.88 (s, 3H), 3.66 (t, J = 4.7 Hz, 4H), 3.12 (dt, J = 12.0, 4.5 Hz, 2H), 3.04 (dt, J = 12.0, 4.5 Hz, 2H), 1.69 (d, J = 14.5 Hz, 1H), 1.54 (s, 3H), 1.52 (d, J = 14.5 Hz, 1H), 1.45 (s, 3H), 1.02 (s, 9H); 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 166.2, 149.4, 149.3, 148.0, 138.4, 127.5, 126.6, 123.8, 111.0, 66.5, 60.2, 57.5, 54.4, 46.8, 32.1, 31.84, 31.80, 31.5; IR (ATR): ṽ (cm ^–1 ) = 1586, 1528, 1479, 1349, 1298, 1256, 1154, 1089, 1050, 1012, 919, 736; HRMS (ESI ⁺ ) calcd. for C ₂₄ H ₃₅ N ₅ O ₆ S ₂ Na ⁺ [M+Na] ⁺ : 576.1921, found: 576.1915. [00399] N-(Morpholino(pyridin-3-yl)((2,4,4-trimethylpentan-2-yl)imin o)-λ6- sulfaneylidene)-4-nitrobenzenesulfonamide (E10) Prepared according to General Procedure C using sulfondiimidoyl fluoride P26 (230 mg, 0.50 mmol, 1.00 equiv.), Ca(NTf2)2 (330 mg, 0.55 mmol, 1.10 equiv.), morpholine (96 mg, 1.10 mmol, 2.20 equiv.) and t-AmylOH (1.00 mL). The reaction was stirred at 60 °C for 36 h. Purification by flash column chromatography (petrol/ethyl acetate, 2:1 to 1:2) afforded sulfondiimidamide E10 as a white solid (240 mg, 0.46 mmol, 92%). mp 126-128 °C (CH2Cl2); Rf 0.33 (petrol/ethyl acetate, 1:2); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.74 (dd, J = 2.5, 0.8 Hz, 1H), 8.65 (dd, J = 4.8, 1.5 Hz, 1H), 8.14 (d, J = 8.9 Hz, 2H), 7.95 (ddd, J = 8.2, 2.5, 1.5 Hz, 1H), 7.78 (d, J = 8.9 Hz, 2H), 7.32 (ddd, J = 8.2, 4.8, 0.8 Hz, 1H), 3.64 (ddd, J = 5.2, 3.8, 1.1 Hz, 4H), 3.11 (dt, J = 12.5, 4.7 Hz, 2H), 3.02 (dt, J = 12.5, 4.7 Hz, 2H), 1.70 (d, J = 14.5 Hz, 1H), 1.54 (s, 3H), 1.53 (d, J = 14.5 Hz, 1H), 1.46 (s, 3H), 1.01 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 152.8, 149.3, 149.0, 148.5, 135.8, 134.3, 127.3, 123.9, 123.4, 66.4, 60.4, 57.3, 46.8, 32.0, 31.8, 31.7, 31.5; IR (ATR): ṽ (cm ^–1 ) = 1528, 1350, 1297, 1257, 1154, 1110, 1089, 1062, 1011, 921, 742; HRMS (ESI ⁺ ) calcd. for C ₂₃ H ₃₃ N ₅ O ₅ S ₂ Na ⁺ [M+Na] ⁺ : 546.1815, found: 546.1808. [00400] N-(Cyclopropyl(morpholino)((2,4,4-trimethylpentan-2-yl)imino )-λ6- sulfaneylidene)-4-nitrobenzenesulfonamide (E11) Prepared according to General Procedure C using sulfondiimidoyl fluoride P27 (390 mg, 0.93 mmol, 1.00 equiv.), Ca(NTf2)2 (614 mg, 1.02 mmol, 1.10 equiv.), morpholine (178 mg, 2.04 mmol, 2.20 equiv.) and t-AmylOH (1.86 mL). The reaction was stirred at 60 °C for 24 h. Purification by flash column chromatography (petrol/ethyl acetate, 3:1 to 1:1) afforded sulfondiimidamide E11 as a white solid (413 mg, 0.85 mmol, 91%). mp 125-127 °C (CH2Cl2); Rf 0.23 (petrol/ethyl acetate, 2:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.25 (d, J = 8.9 Hz, 2H), 8.06 (d, J = 8.9 Hz, 2H), 3.67 (ddd, J = 7.5, 6.0, 3.2 Hz, 4H), 3.28 (ddd, J = 12.0, 6.0, 3.2 Hz, 2H), 3.19 (ddd, J = 12.0, 6.0, 3.2 Hz, 2H), 2.26 (tt, J = 7.6, 4.5 Hz, 1H), 1.44 (d, J = 14.5 Hz, 1H), 1.36 (s, 3H), 1.36 (d, J = 14.5 Hz, 1H), 1.29 (s, 3H), 1.26 (dt, J = 5.3, 2.7 Hz, 2H), 1.01-0.95 (m, 1H), 0.90 (s, 9H), 0.93- 0.83 (m, 1H); 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 150.5, 149.2, 127.4, 123.9, 66.6, 59.5, 57.8, 47.2, 32.0, 31.7, 31.6, 31.3, 29.2, 7.6, 5.6; IR (ATR): ṽ (cm ^–1 ) = 1527, 1349, 1293, 1256, 1149, 1091, 1057, 918, 733; HRMS (ESI ⁺ ) calcd. for C21H35N4O5S2 ⁺ [M+H] ⁺ : 487.2043, found: 487.2045. [00401] N-(Ethyl(morpholino)((2,4,4-trimethylpentan-2-yl)imino)-λ6- sulfaneylidene)-4-nitrobenzenesulfonamide (E12) Prepared according to General Procedure C using sulfondiimidoyl fluoride P28 (245 mg, 0.52 mmol, 1.00 equiv.), Ca(NTf2)2 (343 mg, 0.57 mmol, 1.10 equiv.), t-AmylOH (1.00 mL) and morpholine (100 mg, 1.15 mmol, 2.20 equiv.). The reaction was stirred at 60 °C for 20 h. Ethyl acetate was used for extraction instead of CH2Cl2 because of the better aqueous solubility of this substrate. Purification by flash column chromatography (petrol/ethyl acetate, 3:1 to 1:1) afforded sulfondiimidamide E12 as a white solid (212 mg, 0.45 mmol, 86%). mp 94-96 °C (CH2Cl2); Rf 0.38 (petrol/ethyl acetate, 1:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.30 (d, J = 8.9 Hz, 2H), 8.09 (d, J = 8.9 Hz, 2H), 3.75- 3.66 (m, 4H, major), 3.64-3.59 (m, 4H, minor), 3.58 (q, J = 7.4 Hz, 2H), 3.35-3.29 (m, 4H, major), 3.28-3.24 (m, 4H, minor), 1.52 (d, J = 14.4 Hz, 1H), 1.40 (d, J = 14.4 Hz, 1H), 1.37 (s, 3H), 1.33 (s, 3H), 1.29 (t, J = 7.3 Hz, 3H), 0.98 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 150.2, 149.4, 127.3, 124.1, 67.9 (minor), 67.0 (major), 59.4, 57.8 (minor), 57.5 (major), 50.1, 47.1, 32.1, 32.0, 31.8, 31.4, 8.9; IR (ATR): ṽ (cm ^–1 ) = 2980, 1528, 1350, 1256, 1148, 1091, 1066, 924, 739; HRMS (ESI ⁺ ) calcd. for C20H34N4O5S2Na ⁺ [M+Na] ⁺ : 497.1863, found: 497.1856. [00402] N-((3-Cyano-4-ethoxyphenyl)(morpholino)((2,4,4-trimethylpent an-2- yl)imino)-λ6-sulfaneylidene)-4-nitrobenzenesulfonamide (E13) Prepared according to General Procedure C using sulfondiimidoyl fluoride P30 (510 mg, 0.97 mmol, 1.00 equiv.), Ca(NTf ₂ ) ₂ (642 mg, 1.07 mmol, 1.10 equiv.), morpholine (186 mg, 2.13 mmol, 2.20 equiv.) and t-AmylOH (1.94 mL). The reaction was stirred at 60 °C for 24 h.0.5 M aq. HCl solution was used to quench the reaction (instead of sat. aq. NaCl solution) and the aqueous layers was extracted with ethyl acetate (instead of CH2Cl2). Purification by flash column chromatography (petrol/ethyl acetate, 1:1 to 1:2) afforded sulfondiimidamide E13 as a white solid (546 mg, 0.92 mmol, 95%). mp 183-185 °C (CH2Cl2); Rf 0.58 (petrol/ethyl acetate, 2:3); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.23 (d, J = 8.8 Hz, 2H), 7.88 (d, J = 8.8 Hz, 2H), 7.84- 7.78 (m, 2H), 6.92 (d, J = 8.9 Hz, 1H), 4.19 (q, J = 7.0 Hz, 2H), 3.70 (td, J = 4.1, 1.9 Hz, 4H), 3.10 (dt, J = 12.0, 4.6 Hz, 2H), 3.03 (dt, J = 12.0, 4.6 Hz, 2H), 1.71 (d, J = 14.5 Hz, 1H), 1.56 (d, J = 14.5 Hz, 1H), 1.55 (s, 3H), 1.51 (t, J = 7.0 Hz, 3H), 1.48 (s, 3H), 1.05 (s, 9H); 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 163.3, 149.5, 149.3, 134.2, 134.1, 129.6, 127.5, 124.0, 114.7, 112.1, 102.8, 66.6, 66.0, 60.6, 57.6, 47.0, 32.1, 31.92, 31.89, 31.5, 14.4; IR (ATR): ṽ (cm ^–1 ) = 2980, 1529, 1349, 1294, 1256, 1152, 1063, 920, 735; HRMS (ESI ⁺ ) calcd. for C ₂₇ H ₃₈ N ₅ O ₆ S ₂ ⁺ [M+H] ⁺ : 592.2258, found: 592.2261. [00403] N-(Morpholino(4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol- 1- yl)phenyl)((2,4,4-trimethylpentan-2-yl)imino)-λ6-sulfaneyli dene)-4- nitrobenzenesulfonamide (E14) Prepared according to General Procedure C using sulfondiimidoyl fluoride P31 (401 mg, 0.59 mmol, 1.00 equiv.), Ca(NTf2)2 (390 mg, 0.65 mmol, 1.10 equiv.), morpholine (112 mg, 1.29 mmol, 2.20 equiv.) and t-AmylOH (1.18 mL). The reaction was stirred at 60 °C for 24 h. Purification by flash column chromatography (petrol/ethyl acetate, 3:1 to 1:1) afforded sulfondiimidamide E14 as a white solid (386 mg, 0.52 mmol, 88%). mp 165-167 °C (CH2Cl2); Rf 0.48 (petrol/ethyl acetate, 2:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.11 (d, J = 8.9 Hz, 2H), 7.82 (d, J = 8.9 Hz, 2H), 7.63 (d, J = 8.8 Hz, 2H), 7.37 (d, J = 8.8 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 7.12 (d, J = 8.0 Hz, 2H), 6.72 (s, 1H), 3.65 (t, J = 4.7 Hz, 4H), 3.06 (dt, J = 11.8, 4.5 Hz, 2H), 2.99 (dt, J = 11.8, 4.5 Hz, 2H), 2.38 (s, 3H), 1.72 (d, J = 14.5 Hz, 1H), 1.58 (d, J = 14.5 Hz, 1H), 1.57 (s, 3H), 1.49 (s, 3H), 1.04 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 149.4, 149.3, 145.2, 144.1 (q, J = 38.5 Hz), 142.5, 139.9, 137.2, 129.8, 128.8, 128.7, 127.4, 125.8, 125.2, 123.8, 121.1 (q, J = 269.3 Hz), 106.5, 66.4, 60.4, 57.5, 46.9, 32.0, 31.81, 31.78, 31.5, 21.3; 19F NMR (377 MHz, CDCl3): δ (ppm) = -62.4 (s); IR (ATR): ṽ (cm ^–1 ) = 1529, 1349, 1299, 1236, 1156, 1089, 1062, 918, 733; HRMS (ESI ⁺ ) calcd. for C ₃₅ H ₄₂ F ₃ N ₆ O ₅ S ₂ ⁺ [M+H] ⁺ : 747.2605, found: 747.2604. [00404] N-((4-Fluorophenyl)(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)((2, 4,4- trimethylpentan-2-yl)imino)- λ6-sulfaneylidene)-4-nitrobenzenesulfonamide (E15) Prepared according to General Procedure C using sulfondiimidoyl fluoride P17 (220 mg, 0.47 mmol, 1.00 equiv.), Ca(NTf2)2 (307 mg, 0.51 mmol, 1.10 equiv.), t-AmylOH (0.94 mL) and 1,4-Dioxa-8-azaspiro[4.5]decane (148 mg, 1.03 mmol, 2.20 equiv.). The reaction was stirred at 60 °C for 36 h. Purification by flash column chromatography (petrol/ethyl acetate, 3:1 to 1:1) afforded sulfondiimidamide E15 as a white solid (254 mg, 0.43 mmol, 92%). mp 86-88 °C (CH2Cl2); Rf 0.45 (petrol/ethyl acetate, 2:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.15 (d, J = 8.9 Hz, 2H), 7.78 (d, J = 8.9 Hz, 2H), 7.65- 7.60 (m, 2H), 7.03-6.97 (m, 2H), 3.89 (s, 4H), 3.26 (ddd, J = 11.9, 6.5, 4.5 Hz, 2H), 3.19 (ddd, J = 11.9, 6.5, 4.5 Hz, 1H), 1.76-1.66 (m, 5H), 1.58-1.52 (m, 4H), 1.48 (s, 3H), 1.04 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 164.9 (d, J = 255.6 Hz), 149.6, 149.2, 134.3 (d, J = 3.1 Hz), 130.4 (d, J = 9.2 Hz), 127.5, 123.7, 116.0 (d, J = 22.6 Hz), 106.1, 64.6, 60.1, 57.6, 44.9, 34.9, 31.93, 31.85, 31.8, 31.5; 19F NMR (377 MHz, CDCl3): δ (ppm) = -105.6 (tt, J = 8.0, 4.9 Hz); IR (ATR): ṽ (cm ^–1 ) = 1529, 1349, 1300, 1226, 1153, 1088, 1040; HRMS (ESI ⁺ ) calcd. for C27H37FN4O6S2Na ⁺ [M+Na] ⁺ : 619.2031, found: 619.2027. [00405] N-((4,7-Dihydrothieno[2,3-c]pyridin-6(5H)-yl)(4-fluorophenyl )((2,4,4- trimethylpentan-2-yl)imino)- λ6-sulfaneylidene)-4-nitrobenzenesulfonamide (E16) Prepared according to General Procedure C using sulfondiimidoyl fluoride P17 (115 mg, 0.24 mmol, 1.00 equiv.), Ca(NTf ₂ ) ₂ (160 mg, 0.27 mmol, 1.10 equiv.), t-AmylOH (0.48 mL) and 4,5,6,7-tetrahydrothieno[3,2-c]pyridine (74 mg, 0.53 mmol, 2.20 equiv.). The reaction was stirred at 60 °C for 36 h. Purification by flash column chromatography (petrol/ethyl acetate, 4:1 to 3:1) afforded sulfondiimidamide E16 as a pale-yellow oil (117 mg, 0.20 mmol, 81%). Rf 0.45 (petrol/ethyl acetate, 4:1); 1H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.13 (d, J = 8.8 Hz, 2H), 7.78 (d, J = 8.8 Hz, 2H), 7.74 -7.68 (m, 2H), 7.12 (d, J = 5.2 Hz, 1H), 7.04-6.97 (m, 2H), 6.68 (d, J = 5.2 Hz, 1H), 4.35 (d, J = 15.1 Hz, 1H), 4.20 (d, J = 15.1 Hz, 1H), 3.59 (ddd, J = 12.0, 6.8, 4.9 Hz, 1H), 3.50 (dt, J = 12.0, 5.5 Hz, 1H), 2.94-2.73 (m, 2H), 1.68 (d, J = 14.5 Hz, 1H), 1.57 (d, J = 14.5 Hz, 1H), 1.54 (s, 3H), 1.46 (s, 3H), 1.06 (s, 9H); 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 165.0 (d, J = 256.2 Hz), 149.5, 149.2, 135.0 (d, J = 3.1 Hz), 132.8, 131.1, 130.7 (d, J = 9.2 Hz), 127.5, 124.8, 124.2, 123.7, 116.0 (d, J = 22.6 Hz), 60.2, 57.6, 46.5, 44.1, 31.94, 31.90, 31.8, 31.6, 25.6 (note: for the gem-dimethyl carbons in the tert-octyl group, NC(CH3)2CH2C(CH3)3, 2 peaks were found instead of 1 due to the loss of symmetry caused by chiral sulfur atom); 19F NMR (377 MHz, CDCl3): δ (ppm) = -105.2 (tt, J = 8.0, 5.0 Hz); IR (ATR): ṽ (cm ^–1 ) = 2980, 2889, 1383, 1252, 1153, 1088, 955; HRMS (ESI ⁺ ) calcd. for C27H33FN4O4S3Na ⁺ [M+Na] ⁺ : 615.1540, found: 615.1536. [00406] N-((4-(2-Chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-1-y l)(4- fluorophenyl)((2,4,4-trimethylpentan-2-yl)imino)- λ6-sulfaneylidene)-4- nitrobenzenesulfonamide (E17) Prepared according to General Procedure C using sulfondiimidoyl fluoride P17 (238 mg, 0.50 mmol, 1.00 equiv.), Ca(NTf2)2 (332 mg, 0.55 mmol, 1.10 equiv.), t-AmylOH (1.0 mL) and Amoxapine (345 mg, 1.10 mmol, 2.20 equiv.). The reaction was stirred at 60 °C for 24 h. Purification by flash column chromatography (petrol/ethyl acetate, 5:1 to 4:1) afforded sulfondiimidamide E17 as a pale-yellow solid (350 mg, 0.46 mmol, 91%). mp 68-70 °C (CH2Cl2); Rf 0.50 (petrol/ethyl acetate, 4:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.19 (d, J = 8.8 Hz, 2H), 7.85 (d, J = 8.8 Hz, 2H), 7.72 -7.66 (m, 2H), 7.39 (dd, J = 8.6, 2.6 Hz, 1H), 7.23-7.01 (m, 8H), 3.59 (br. s, 4H), 3.25 (br. s, 4H), 1.74 (d, J = 14.5 Hz, 1H), 1.59 (s, 3H), 1.59 (d, J = 14.5 Hz, 1H), 1.53 (s, 3H), 1.08 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 165.1 (d, J = 256.3 Hz), 159.5, 158.6, 151.9, 149.5, 149.4, 139.1, 133.9 (d, J = 2.3 Hz), 133.3, 130.6, 130.5 (d, J = 9.5 Hz), 128.9, 127.5, 127.1, 126.0, 125.6, 124.3, 123.9, 123.1, 120.3, 116.3 (d, J = 22.6 Hz), 60.4, 57.6, 47.6, 46.5, 32.02, 31.96, 31.9, 31.5; 19F NMR (377 MHz, CDCl3): δ (ppm) = -104.9 (s); IR (ATR): ṽ (cm ^–1 ) = 2980, 2888, 1383, 1251, 1153, 1086, 954; HRMS (ESI ⁺ ) calcd. for C37H41ClFN6O5S2 ⁺ [M+H] ⁺ : 767.2247, found: 767.2237. [00407] N-((4-(Benzo[d]isothiazol-3-yl)piperazin-1-yl)(4-fluoropheny l)((2,4,4- trimethylpentan-2-yl)imino)- λ6-sulfaneylidene)-4-nitrobenzenesulfonamide (E18) Prepared according to General Procedure C using sulfondiimidoyl fluoride P17 (180 mg, 0.38 mmol, 1.00 equiv.), Ca(NTf2)2 (251 mg, 0.42 mmol, 1.10 equiv.), t-AmylOH (0.76 mL) and 3- (piperazin-1-yl)benzo[d]isothiazole (184 mg, 0.84 mmol, 2.20 equiv.). The reaction was stirred at 60 °C for 36 h. Purification by flash column chromatography (petrol/ethyl acetate, 4:1 to 2:1) afforded sulfondiimidamide E18 as a pale-yellow solid (238 mg, 0.35 mmol, 93%). mp 66-68 °C (CH2Cl2); Rf 0.54 (petrol/ethyl acetate, 2:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.20 (d, J = 8.8 Hz, 2H), 7.86 (d, J = 8.8 Hz, 2H), 7.81 (dt, J = 8.1, 1.0 Hz, 1H), 7.79 (dt, J = 8.1, 1.0 Hz, 1H), 7.75-7.70 (m, 2H), 7.47 (ddd, J = 8.1, 7.0, 1.1 Hz, 1H), 7.34 (ddd, J = 8.1, 7.0, 1.1 Hz, 1H), 7.10-7.05 (m, 2H), 3.60 (ddd, J = 12.7, 6.5, 3.3 Hz, 2H), 3.54 (ddd, J = 12.7, 6.5, 3.3 Hz, 2H), 3.39 (ddd, J = 10.0, 6.4, 3.3 Hz, 2H), 3.33 (ddd, J = 10.0, 6.4, 3.3 Hz, 2H), 1.75 (d, J = 14.5 Hz, 1H), 1.60 (s, 3H), 1.60 (d, J = 14.5 Hz, 1H), 1.54 (s, 3H), 1.08 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 165.0 (d, J = 256.0 Hz), 163.0, 152.9, 149.5, 149.3, 133.8 (d, J = 3.1 Hz), 130.6 (d, J = 9.2 Hz), 127.9, 127.6, 127.5, 124.3, 123.8, 123.5, 120.8, 116.1 (d, J = 22.6 Hz), 60.3, 57.6, 49.9, 46.5, 32.0, 31.94, 31.87, 31.5; 19F NMR (377 MHz, CDCl3): δ (ppm) = -105.1 (tt, J = 8.0, 4.9 Hz); IR (ATR): ṽ (cm ^–1 ) = 1528, 1489, 1383, 1349, 1302, 1261, 1230, 1153, 1087, 1052, 925, 737; HRMS (ESI ⁺ ) calcd. for C31H38FN6O4S3 ⁺ [M+H] ⁺ : 673.2095, found: 673.2093. [00408] N-((4-(6-Fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)(4- fluorophenyl)((2,4,4-trimethylpentan-2-yl)imino)- λ6-sulfaneylidene)-4- nitrobenzenesulfonamide (E19) Prepared according to General Procedure C using sulfondiimidoyl fluoride P17 (180 mg, 0.38 mmol, 1.00 equiv.), Ca(NTf2)2 (251 mg, 0.42 mmol, 1.10 equiv.), t-AmylOH (0.76 mL) and 6- fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (184 mg, 0.84 mmol, 2.20 equiv.). The reaction was stirred at 60 °C for 36 h. Purification by flash column chromatography (petrol/ethyl acetate, 4:1 to 2:1) afforded sulfondiimidamide E19 as a white solid (220 mg, 0.33 mmol, 86%). mp 78-80 °C (CH2Cl2); Rf 0.77 (petrol/ethyl acetate, 2:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.16 (d, J = 8.8 Hz, 2H), 7.82 (d, J = 8.8 Hz, 2H), 7.73- 7.68 (m, 2H), 7.54 (dd, J = 8.7, 5.0 Hz, 1H), 7.21 (dd, J = 8.4, 2.1 Hz, 1H), 7.07-7.01 (m, 3H), 4.09-4.02 (m, 1H), 3.89-3.83 (m, 1H), 3.10 (tt, J = 11.0, 3.9 Hz, 1H), 2.83 (td, J = 11.5, 2.5 Hz, 1H), 2.53 (td, J = 11.5, 2.5 Hz, 1H), 2.21-2.11 (m, 2H), 2.09-1.92 (m, 2H), 1.70 (d, J = 14.5 Hz, 1H), 1.56 (d, J = 14.5 Hz, 1H), 1.56 (s, 3H), 1.50 (s, 3H), 1.05 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 164.9 (d, J = 255.9 Hz), 164.3 (d, J = 251.5 Hz), 163.9 (d, J = 13.5 Hz), 159.9, 149.6, 149.2, 134.2 (d, J = 2.3 Hz), 130.5 (d, J = 9.1 Hz), 127.5, 123.8, 122.0 (d, J = 11.2 Hz), 117.1, 116.1 (d, J = 22.5 Hz), 112.8 (d, J = 25.5 Hz), 97.6 (d, J = 26.9 Hz), 60.1, 57.6, 47.8, 44.9, 33.5, 31.90, 31.86, 31.8, 31.5, 30.5, 29.8; 19F NMR (377 MHz, CDCl3): δ (ppm) = -105.3 (tt, J = 8.0, 4.9 Hz), -108.8 (td, J = 8.6, 5.1 Hz); IR (ATR): ṽ (cm ^–1 ) = 1528, 1349, 1298, 1269, 1229, 1153, 1087, 1050, 913, 839, 736; HRMS (ESI ⁺ ) calcd. for C32H38F2N5O5S2 ⁺ [M+H] ⁺ : 674.2277, found: 674.2272. [00409] N-((4-Fluorophenyl)(4-(pyrimidin-2-yl)piperazin-1-yl)((2,4,4 - trimethylpentan-2-yl)imino)-λ6-sulfaneylidene)-4-nitrobenze nesulfonamide (E20) Prepared according to General Procedure C using sulfondiimidoyl fluoride P17 (86 mg, 0.18 mmol, 1.00 equiv.), Ca(NTf2)2 (120 mg, 0.20 mmol, 1.10 equiv.), t-AmylOH (0.36 mL) and 2- (piperazin-1-yl)pyrimidine (66 mg, 0.40 mmol, 2.20 equiv.). The reaction was stirred at 60 °C for 36 h. Purification by flash column chromatography (petrol/ethyl acetate, 2:1 to 1:1) afforded sulfondiimidamide E20 as a white solid (99 mg, 0.16 mmol, 88%). mp 176-178 °C (CH2Cl2); Rf 0.31 (petrol/ethyl acetate, 2:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.25 (d, J = 4.8 Hz, 2H), 8.17 (d, J = 8.8 Hz, 2H), 7.84 (d, J = 8.8 Hz, 2H), 7.69-7.63 (m, 2H), 7.05-6.98 (m, 2H), 6.50 (t, J = 4.8 Hz, 1H), 3.86 (ddd, J = 6.2, 4.1, 2.2 Hz, 4H), 3.22-3.08 (m, 4H), 1.72 (d, J = 14.4 Hz, 1H), 1.58 (s, 3H), 1.57 (d, J = 14.5 Hz, 1H), 1.51 (s, 3H), 1.06 (s, 9H); 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 165.0 (d, J = 256.1 Hz), 161.3, 157.8, 149.5, 149.3, 133.7 (d, J = 3.1 Hz), 130.6 (d, J = 9.2 Hz), 127.5, 123.8, 116.1 (d, J = 22.7 Hz), 110.9, 60.3, 57.6, 46.7, 43.6, 32.0, 31.93, 31.87, 31.5; 19F NMR (377 MHz, CDCl ₃ ): δ (ppm) = -105.2 (tt, J = 8.0, 4.8 Hz); IR (ATR): ṽ (cm ^–1 ) = 1585, 1528, 1486, 1349, 1300, 1260, 1227, 1153, 1086, 1053, 950, 901, 732; HRMS (ESI ⁺ ) calcd. for C ₂₈ H ₃₇ FN ₇ O ₄ S ₂ ⁺ [M+H] ⁺ : 618.2327, found: 618.2319. [00410] N-(((Cyclohexylmethyl)(methyl)amino)(4-fluorophenyl)((2,4,4- trimethylpentan-2-yl)imino)- λ6-sulfaneylidene)-4-nitrobenzenesulfonamide (E21) Prepared according to General Procedure C using sulfondiimidoyl fluoride P17 (153 mg, 0.32 mmol, 1.00 equiv.), Ca(NTf2)2 (213 mg, 0.36 mmol, 1.10 equiv.), t-AmylOH (0.65 mL) and 1- cyclohexyl-N-methylmethanamine (90 mg, 0.71 mmol, 2.20 equiv.). The reaction was stirred at 60 °C for 36 h. Purification by flash column chromatography (petrol/ethyl acetate, 5:1 to 4:1) afforded sulfondiimidamide E21 as a pale-yellow solid (180 mg, 0.31 mmol, 96%). mp 87-89 °C (CH2Cl2); Rf 0.67 (petrol/ethyl acetate, 4:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.17 (d, J = 8.8 Hz, 2H), 7.77 (d, J = 8.8 Hz, 2H), 7.70- 7.64 (m, 2H), 7.06-6.98 (m, 2H), 3.32 (dd, J = 13.0, 8.0 Hz, 1H), 2.87 (dd, J = 13.0, 6.4 Hz, 1H), 2.56 (s, 3H), 1.77-1.61 (m, 5H), 1.69 (d, J = 14.5 Hz, 1H), 1.59-1.51 (m, 1H), 1.57 (d, J = 14.5 Hz, 1H), 1.54 (s, 3H), 1.46 (s, 3H), 1.26-1.12 (m, 3H), 1.05 (s, 9H), 0.95-0.83 (m, 2H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 164.8 (d, J = 255.4 Hz), 149.9, 149.2, 135.4 (d, J = 3.2 Hz), 130.7 (d, J = 9.2 Hz), 127.3, 123.7, 115.9 (d, J = 22.6 Hz), 59.9, 58.9, 57.6, 37.0, 34.7, 31.93, 31.9031.88, 31.7, 31.3, 31.0, 26.4, 25.9, 25.8; 19F NMR (377 MHz, CDCl3): δ (ppm) = -106.0 (tt, J = 8.1, 5.0 Hz); IR (ATR): ṽ (cm ^–1 ) = 2980, 1528, 1349, 1230, 1152, 1088, 1051; HRMS (ESI ⁺ ) calcd. for C ₂₈ H ₄₁ FN ₄ O ₄ S ₂ Na ⁺ [M+Na] ⁺ : 603.2445, found: 603.2435. [00411] N-((4-Fluorophenyl)(pyridin-3-ylamino)((2,4,4-trimethylpenta n-2- yl)imino)-λ6-sulfaneylidene)-4-nitrobenzenesulfonamide (E22) Prepared according to General Procedure C using sulfondiimidoyl fluoride P17 (146 mg, 0.31 mmol, 1.00 equiv.), Ca(NTf2)2 (205 mg, 0.34 mmol, 1.10 equiv.), t-AmylOH (0.62 mL) and 3- aminopyridine (64 mg, 0.68 mmol, 2.20 equiv.). The reaction was stirred at 60 °C for 30 h. Purification by flash column chromatography (petrol/ethyl acetate, 1:1) afforded sulfondiimidamide E22 as a pale-yellow oil (136 mg, 0.25 mmol, 81%). Rf 0.25 (petrol/ethyl acetate, 2:1); 1H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.47 (dd, J = 2.7, 0.7 Hz, 1H), 8.23-8.18 (m, 2H), 8.15 (dd, J = 4.8, 1.4 Hz, 1H), 7.97 (d, J = 8.9 Hz, 2H), 7.82 (d, J = 8.9 Hz, 2H), 7.44 (ddd, J = 8.2, 2.7, 1.4 Hz, 1H), 7.23-7.16 (m, 2H), 7.09 (ddd, J = 8.2, 4.8, 0.7 Hz, 1H), 6.11 (br. s, 1H) 1.39 (s, 2H), 1.16 (s, 3H), 1.10 (s, 3H), 0.85 (s, 9H); 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 165.7 (d, J = 258.0 Hz), 149.5, 148.0, 143.5, 142.0, 140.2, 136.2 (d, J = 3.3 Hz), 131.6 (d, J = 9.5 Hz), 130.9, 128.2, 123.9, 123.6, 116.7 (d, J = 22.8 Hz), 61.6, 56.5, 31.6, 31.5, 29.3, 28.7; 19F NMR (377 MHz, CDCl3): δ (ppm) = -103.13 (tt, J = 8.0, 4.8 Hz); IR (ATR): ṽ (cm ^–1 ) = 1528, 1349, 1305, 1235, 1156, 1087, 733; HRMS (ESI ⁺ ) calcd. for C25H31FN5O4S2 ⁺ [M+H] ⁺ : 548.1796, found: 548.1792. [00412] N-((4-Fluorophenyl)(1H-imidazol-1-yl)((2,4,4-trimethylpentan -2-yl)imino)- λ6-sulfaneylidene)-4-nitrobenzenesulfonamide (E23) Sulfondiimidoyl fluoride P17 (735 mg, 1.55 mmol, 1.00 equiv.), Ca(NTf ₂ ) ₂ (1.02 g, 1.71 mmol, 1.10 equiv.) and imidazole (633 mg, 9.30 mmol, 6.0 equiv.) were added to an oven-dried 25 mL round-bottom flask and dissolved in anhydrous t-AmylOH (3.10 mL). The reaction was sealed and stirred at 65 °C for 12 h. The crude product was purified by flash column chromatography (petrol/ethyl acetate, 4:1 to 2:1 to 1:2) without an aqueous workup to afford sulfondiimidamide E23 as a white solid (710 mg, 1.36 mmol, 88%). mp 160-162 °C (CH ₂ Cl ₂ ); Rf 0.62 (petrol/ethyl acetate, 1:1); 1H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.20 (d, J = 9.0 Hz, 2H), 8.04 (t, J = 1.1 Hz, 1H), 7.77 (d, J = 9.0 Hz, 2H), 7.61-7.57 (m, 2H), 7.13 (t, J = 1.5 Hz, 1H), 7.09-7.03 (m, 3H), 1.76 (d, J = 14.8 Hz, 1H), 1.62 (s, 3H), 1.59 (d, J = 14.8 Hz, 1H), 1.33 (s, 3H), 1.08 (s, 9H); 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 165.7 (d, J = 259.3 Hz), 149.8, 148.3, 137.9, 135.1 (d, J = 3.2 Hz), 131.6, 130.3 (d, J = 9.8 Hz), 127.5, 124.1, 117.6, 116.8 (d, J = 23.1 Hz), 63.1, 57.2, 31.9, 31.8, 31.3, 30.9; 19F NMR (377 MHz, CDCl3): δ (ppm) = -101.7 (tt, J = 7.7, 4.8 Hz); IR (ATR): ṽ (cm ^–1 ) = 1530, 1350, 1305, 1158, 1085, 1024, 735; HRMS (ESI ⁺ ) calcd. for C23H28FN5O4S2Na ⁺ [M+Na] ⁺ : 544.1459, found: 544.1461. [00413] N-(((Bis(dimethylamino)methylene)amino)(4-fluorophenyl)((2,4 ,4- trimethylpentan-2-yl)imino)-λ6-sulfaneylidene)-4-nitrobenze nesulfonamide (E24) Prepared according to General Procedure C using sulfondiimidoyl fluoride P17 (132 mg, 0.28 mmol, 1.00 equiv.), Ca(NTf ₂ ) ₂ (184 mg, 0.31 mmol, 1.10 equiv.), t-AmylOH (0.70 mL) and 1,1,3,3-tetramethylguanidine (97 mg, 0.84 mmol, 3.00 equiv.). The reaction was stirred at 80 °C for 24 h. Purification by flash column chromatography (petrol/ethyl acetate, 3:1 to 1:1 to 1:3) afforded sulfondiimidamide E24 as a colourless oil (135 mg, 0.24 mmol, 85%). Rf 0.50 (petrol/ethyl acetate, 1:2); 1H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.12 (d, J = 8.9 Hz, 2H), 7.91-7.84 (m, 4H), 6.94-6.87 (m, 2H), 2.91 (s, 12H), 1.43 (d, J = 14.4 Hz, 1H), 1.34 (d, J = 14.3 Hz, 1H), 1.27 (s, 3H), 1.20 (s, 3H), 0.83 (s, 9H); 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 163.8 (d, J = 252.6 Hz), 161.5, 151.4, 148.7, 143.8 (d, J = 3.0 Hz), 129.0 (d, J = 8.8 Hz), 127.6, 123.3, 114.9 (d, J = 22.3 Hz), 59.3, 57.8, 41.1, 31.8, 31.7, 31.6, 31.3; 19F NMR (377 MHz, CDCl3): δ (ppm) = -108.6 (tt, J = 8.6, 5.2 Hz); IR (ATR): ṽ (cm ^–1 ) =1521, 1396, 1348, 1218, 1143, 1088, 1039, 729; HRMS (ESI ⁺ ) calcd. for C25H38FN6O4S2 ⁺ [M+H] ⁺ : 569.2374, found: 569.2370. [00414] The following two compounds were prepared according to General Procedure C using sulfondiimidoyl fluoride P17 (380 mg, 0.80 mmol, 1.00 equiv.), Ca(NTf2)2 (530 mg, 0.88 mmol, 1.10 equiv.), t-AmylOH (1.60 mL) and (S)-(+)-2-(methoxymethyl)pyrrolidine (203 mg, 1.76 mmol, 2.0 equiv.). The reaction was stirred at 70 °C for 36 h. Purification by flash column chromatography (CH2Cl2/ethyl acetate, 20:1 to 15:1) afforded sulfondiimidamide E25 as a white solid (204 mg, 0.36 mmol, 45%) and sulfondiimidamide E26 as a colourless oil (206 mg, 0.36 mmol, 45%). [00415] N-((R)-(4-Fluorophenyl)((S)-2-(methoxymethyl)pyrrolidin-1-yl )((2,4,4- trimethylpentan-2-yl)imino)- λ6-sulfaneylidene)-4-nitrobenzenesulfonamide (E25) [00416] N-((S)-(4-Fluorophenyl)((S)-2-(methoxymethyl)pyrrolidin-1-yl )((2,4,4- trimethylpentan-2-yl)imino)- λ6-sulfaneylidene)-4-nitrobenzenesulfonamide (E26) Diastereoisomer 1 (Sulfur stereochemistry not known) mp 108-110 °C (CH2Cl2); Rf 0.60 (CH ₂ Cl ₂ /ethyl acetate, 15:1); 1H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.08 (d, J = 8.8 Hz, 2H), 7.82-7.75 (m, 2H), 7.54 (d, J = 8.8 Hz, 2H), 7.03-6.96 (m, 2H), 4.32 (ddt, J = 8.0, 5.5, 2.8 Hz, 1H), 3.47 (dd, J = 9.3, 5.4 Hz, 1H), 3.34 (dd, J = 9.3, 2.6 Hz, 1H), 3.23-3.15 (m, 1H), 3.20 (s, 3H), 2.73-2.67 (m, 1H), 2.03- 1.82 (m, 4H), 1.68 (d, J = 14.5 Hz, 1H), 1.62 (s, 3H), 1.58 (d, J = 14.5 Hz, 1H), 1.49 (s, 3H), 1.04 (s, 9H); 13C NMR (101 MHz, (CD3)2CO): δ (ppm) = 165.7 (d, J = 252.7 Hz), 150.8, 150.0, 137.0 (d, J = 2.9 Hz), 132.5 (d, J = 9.5 Hz), 128.0, 124.5, 116.5 (d, J = 23.0 Hz), 75.3, 61.0, 59.9, 59.0, 58.1, 46.9, 32.6, 32.4, 32.3, 32.2, 29.7, 24.7; 19F NMR (377 MHz, CDCl ₃ ): δ (ppm) = -106.1 (tt, J = 8.0, 5.0 Hz); IR (ATR): ṽ (cm ^–1 ) =1718, 1529, 1489, 1349, 1300, 1228, 1155, 1088, 1052, 1030, 997; HRMS (ESI ⁺ ) calcd. for C ₂₆ H ₃₈ FN ₄ O ₅ S ₂ ⁺ [M+H] ⁺ : 569.2262, found: 569.2264; [α]^ ^^: -126.4° (c = 1.0, CHCl ₃ ). Diastereoisomer 2 (Sulfur stereochemistry not known) Rf 0.46 (CH ₂ Cl ₂ /ethyl acetate, 15:1); 1H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.14 (d, J = 8.8 Hz, 2H), 7.77 (d, J = 8.8 Hz, 2H), 7.69- 7.63 (m, 2H), 7.00-6.94 (m, 2H), 4.14 (tt, J = 7.2, 3.6 Hz, 1H), 3.57 (dd, J = 9.2, 3.3 Hz, 1H), 3.38 (dd, J = 9.2, 6.8 Hz, 1H), 3.28 (s, 3H), 3.17-3.10 (m, 1H), 3.00-2.93 (m, 1H), 1.93-1.78 (m, 3H), 1.67 (d, J = 14.5 Hz, 1H), 1.56 (s, 3H), 1.55 (d, J = 14.4 Hz, 1H), 1.47 (s, 3H), 1.46- 1.39 (m, 1H), 1.03 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 164.7 (d, J = 255.4 Hz), 149.9, 149.1, 136.3 (d, J = 3.1 Hz), 130.4 (d, J = 9.2 Hz), 127.3, 123.7, 115.8 (d, J = 22.6 Hz), 75.4, 62.9, 60.1, 59.0, 57.5, 47.7, 31.9, 31.8, 31.4, 31.3, 28.8, 24.5; 19F NMR (377 MHz, CDCl3): δ (ppm) = -105.9 (tt, J = 8.0, 5.0 Hz); IR (ATR): ṽ (cm ^–1 ) = 1589, 1529, 1489, 1350, 1300, 1229, 1154, 1089, 1056, 1030; HRMS (ESI ⁺ ) calcd. for C26H38FN4O5S2 ⁺ [M+H] ⁺ : 569.2262, found: 569.2256; [α]^ ^^: +17.0° (c = 1.0, CHCl3). [00417] General Procedure D - Sulfondiimidamide Synthesis An oven-dried round-bottom flask containing the imidazole derivative E23 (1.00 equiv.) was sealed and subjected to three N2 evacuation/refill cycles before anhydrous CH2Cl2 (0.3 M) was added. The solution was cooled to 0 °C before MeOTf (1.05 equiv.) was added. The reaction was warmed to room temperature and stirred for 30 min. Then the amine (2.10 equiv.) was added and the reaction was stirred at room temperature for another 30 min before being quenched with sat. aq. NaCl solution. CH ₂ Cl ₂ was added and the organic layer was separated. The aqueous layers were extracted with CH2Cl2 × 2. The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by flash column to afford the sulfondiimidamide product. [00418] N-((Butylamino)(4-fluorophenyl)((2,4,4-trimethylpentan-2-yl) imino)-λ6- sulfaneylidene)-4-nitrobenzenesulfonamide (E27) An oven-dried 10 mL round-bottom flask containing E23 (107 mg, 0.21 mmol, 1.00 equiv.) was sealed and subjected to three N2 evacuation/refill cycles before anhydrous CH2Cl2 (0.70 mL) was added. The solution was cooled to 0 °C before MeOTf (25 µL, 0.22 mmol, 1.05 equiv.) was added. The reaction was warmed to room temperature and stirred for 30 min. Then the n-butyl amine (32 mg, 0.43 mmol, 2.10 equiv.) was added and the reaction was stirred at room temperature for another 30 min before being quenched with sat. aq. NaCl solution (50 mL). CH2Cl2 (20 mL) was added and the organic layer was separated. The aqueous layers was extracted with CH2Cl2 (2 × 20 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by flash column chromatography (petrol/ethyl acetate, 3:1) to afford sulfondiimidamide E27 as a white solid (105 mg, 0.20 mmol, 97%). mp 81-83 °C (CH2Cl2); Rf 0.63 (petrol/ethyl acetate, 2:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.13 (d, J = 8.9 Hz, 2H), 7.85-7.78 (m, 4H), 7.03- 6.97 (m, 2H), 5.77 (br. s, 1H), 2.98 (dt, J = 12.2, 7.3 Hz, 1H), 2.64 (dt, J = 12.2, 7.3 Hz, 1H), 1.64 (d, J = 14.5 Hz, 1H), 1.56-1.43 (m, 9H), 1.33-1.23 (m, 2H), 1.02 (s, 9H), 0.84 (t, J = 7.3 Hz, 3H); 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 164.9 (d, J = 255.9 Hz), 149.3, 149.2, 135.4 (d, J = 2.0 Hz), 130.7 (d, J = 9.2 Hz), 127.7, 123.7, 116.0 (d, J = 22.7 Hz), 60.2, 57.6, 41.6, 31.87, 31.86, 31.6, 31.5, 31.3, 20.1, 13.7; 19F NMR (377 MHz, CDCl ₃ ): δ (ppm) = -105.5 (s); IR (ATR): ṽ (cm ^–1 ) = 1529, 1348, 1290, 1268, 1233, 1146, 1091, 1025, 1006, 731; HRMS (ESI ⁺ ) calcd. for C ₂₄ H ₃₆ FN ₄ O ₄ S ₂ ⁺ [M+H] ⁺ : 527.2157, found: 527.2156. [00419] N-((Allylamino)(4-fluorophenyl)((2,4,4-trimethylpentan-2-yl) imino)-λ6- sulfaneylidene)-4-nitrobenzenesulfonamide (E28) Prepared according to General Procedure D using E23 (96 mg, 0.18 mmol, 1.00 equiv.), CH2Cl2 (0.60 mL), MeOTf (22 µL, 0.19 mmol, 1.05 equiv.) and allylamine (22 mg, 0.39 mmol, 2.10 equiv.). Purification by flash column chromatography (petrol/ethyl acetate, 3:1) afforded E28 as a white solid (75 mg, 0.15 mmol, 80%). mp 95-97 °C (CH2Cl2); Rf 0.43 (petrol/ethyl acetate, 2:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.13 (d, J = 8.9 Hz, 2H), 7.88-7.78 (m, 2H), 7.81 (d, J = 8.9 Hz, 2H), 7.05-6.98 (m, 2H), 6.15-5.50 (m, 2H), 5.22 (d, J = 17.0 Hz, 1H), 5.14 (dd, J = 10.3, 1.3 Hz, 1H), 3.74- 3.12 (m, 2H), 1.67- 1.37 (m, 8H), 1.01 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 165.0 (d, J = 256.1 Hz), 149.3, 149.2, 135.5, 132.6, 130.7 (d, J = 9.3 Hz), 127.7, 123.7, 118.1, 116.1 (d, J = 22.7 Hz), 60.4, 57.5, 44.3, 31.9, 31.8, 31.2; 19F NMR (377 MHz, CDCl3): δ (ppm) = -105.1 (s); IR (ATR): ṽ (cm ^–1 ) = 2980, 1528, 1349, 1230, 1148, 1088, 1004, 731; HRMS (ESI ⁺ ) calcd. for C23H31FN4O4S2Na ⁺ [M+Na] ⁺ : 533.1663, found: 533.1660. [00420] N-((Cyclopropylamino)(4-fluorophenyl)((2,4,4-trimethylpentan -2- yl)imino)-λ6-sulfaneylidene)-4-nitrobenzenesulfonamide (E29) Prepared according to General Procedure D using E23 (98 mg, 0.19 mmol, 1.00 equiv.), CH ₂ Cl ₂ (0.62 mL), MeOTf (22 µL, 0.20 mmol, 1.05 equiv.) and cyclopropylamine (23 mg, 0.39 mmol, 2.10 equiv.). Purification by flash column chromatography (petrol/ethyl acetate, 3:1) afforded E29 as a pale-yellow solid (89 mg, 0.17 mmol, 93%). mp 88-90 °C (CH ₂ Cl ₂ ); Rf 0.50 (petrol/ethyl acetate, 3:1); 1H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.18 (d, J = 8.8 Hz, 2H), 7.93-7.87 (m, 2H), 7.85 (d, J = 8.8 Hz, 2H), 7.09-7.02 (m, 2H), 6.40-5.12 (br. s, 1H), 2.47 (br. s, 1H), 1.66 (d, J = 14.6 Hz, 1H), 1.58 (d, J = 14.8 Hz, 1H), 1.50 (s, 3H), 1.46 (s, 3H), 1.03 (s, 9H), 0.66-0.53 (m, 2H), 0.50- 0.41 (m, 1H), 0.27 (br. s, 1H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 165.0 (d, J = 256.0 Hz), 149.4, 149.0, 136.2 (d, J = 2.0 Hz), 131.0 (d, J = 9.3 Hz), 127.7, 123.7, 115.9 (d, J = 22.7 Hz), 60.3, 57.3, 31.88, 31.85, 31.2, 25.0, 6.3; 19F NMR (377 MHz, CDCl3): δ (ppm) = -105.3 (s); IR (ATR): ṽ (cm ^–1 ) = 2980, 1383, 1252, 1149, 1088, 955; HRMS (ESI ⁺ ) calcd. for C23H31FN4O4S2Na ⁺ [M+Na] ⁺ : 533.1663, found: 533.1656. [00421] N-((tert-Butylamino)(4-fluorophenyl)((2,4,4-trimethylpentan- 2-yl)imino)- λ6-sulfaneylidene)-4-nitrobenzenesulfonamide (E30) Prepared according to General Procedure D using E23 (97 mg, 0.19 mmol, 1.00 equiv.), CH ₂ Cl ₂ (0.62 mL), MeOTf (22 µL, 0.20 mmol, 1.05 equiv.) and tert-butylamine (29 mg, 0.39 mmol, 2.10 equiv.). Purification by flash column chromatography (petrol/ethyl acetate, 3:1) afforded E30 as a white solid (80 mg, 0.15 mmol, 82%). mp 106-108 °C (CH ₂ Cl ₂ ); Rf 0.50 (petrol/ethyl acetate, 3:1); 1H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.22 (d, J = 8.8 Hz, 2H), 7.98-7.94 (m, 2H), 7.90 (d, J = 8.8 Hz, 2H), 7.08-7.03 (m, 2H), 6.06 (br. s, 1H), 1.66-1.57 (m, 2H), 1.48-1.23 (m, 15H), 1.00 (s, 9H); 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 164.9 (d, J = 255.5 Hz), 149.6, 149.4, 140.2, 130.6 (d, J = 9.3 Hz), 127.5, 123.9, 115.9 (d, J = 22.6 Hz), 60.8, 57.3, 56.4, 31.9, 31.8, 31.1, 30.6; 19F NMR (377 MHz, CDCl ₃ ): δ (ppm) = -106.4 (tt, J = 8.2, 4.9 Hz); IR (ATR): ṽ (cm ^–1 ) =1531, 1348, 1286, 1227, 1144, 1091, 1045, 965, 744; HRMS (ESI ⁺ ) calcd. for C ₂₄ H ₃₅ FN ₄ O ₄ S ₂ Na ⁺ [M+Na] ⁺ : 549.1976, found: 549.1974. [00422] N-((2,3-Dihydro-1H-pyrrolo[2,3-b]pyridin-1-yl)(4-fluoropheny l)((2,4,4- trimethylpentan-2-yl)imino)-λ6-sulfaneylidene)-4-nitrobenze nesulfonamide (E31) Prepared according to General Procedure D using E23 (93 mg, 0.18 mmol, 1.00 equiv.), CH2Cl2 (0.60 mL), MeOTf (21 µL, 0.19 mmol, 1.05 equiv.) and a solution of 2,3-dihydro-7- azaindole (45 mg, 0.38 mmol, 2.10 equiv) in CH2Cl2 (0.6 mL). Purification by flash column chromatography (petrol/ethyl acetate, 3:1 to 1:1) afforded E31 as a white solid (88 mg, 0.15 mmol, 85%). mp 118-120 °C (CH2Cl2); Rf 0.40 (petrol/ethyl acetate, 2:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.09 (d, J = 8.8 Hz, 2H), 7.83-7.78 (m, 2H), 7.74 (ddd, J = 5.2, 1.8, 0.9 Hz, 1H), 7.70 (d, J = 8.8 Hz, 2H), 7.34 (dq, J = 7.3, 1.3 Hz, 1H), 6.96-6.89 (m, 2H), 6.69 (dd, J = 7.3, 5.2 Hz, 1H), 4.51 (td, J = 10.5, 6.5 Hz, 1H), 4.26 (td, J = 10.5, 7.3 Hz, 1H), 3.21-3.01 (m, 2H), 1.63 (d, J = 14.5 Hz, 1H), 1.57 (s, 3H), 1.49 (d, J = 14.5 Hz, 1H), 1.35 (s, 3H), 1.02 (s, 9H); 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 164.8 (d, J = 255.3 Hz), 156.3, 149.8, 149.1, 146.5, 136.6 (d, J = 3.1 Hz), 133.1, 130.9 (d, J = 9.2 Hz), 127.4, 124.4, 123.6, 117.7, 115.5 (d, J = 23.0 Hz), 60.7, 57.2, 51.0, 31.83, 31.81, 31.75, 31.4, 25.4; 19F NMR (377 MHz, CDCl ₃ ): δ (ppm) = -105.8 (tt, J = 8.1, 5.0 Hz); IR (ATR): ṽ (cm ^–1 ) = 1528, 1415, 1349, 1301, 1230, 1152, 1088, 1043, 949, 736; HRMS (ESI ⁺ ) calcd. for C ₂₇ H ₃₃ FN ₅ O ₄ S ₂ ⁺ [M+H] ⁺ : 574.1953, found: 574.1946. [00423] N-((4-Fluorophenyl)((5-methylisoxazol-3-yl)amino)((2,4,4- trimethylpentan-2-yl)imino)-λ6-sulfaneylidene)-4-nitrobenze nesulfonamide (E32) Prepared according to General Procedure D using E23 (113 mg, 0.22 mmol, 1.00 equiv.), CH2Cl2 (0.72 mL), MeOTf (26 µL, 0.23 mmol, 1.05 equiv.) and a solution of 3-amino-5- methylisoxazole (45 mg, 0.46 mmol, 2.10 equiv) in CH2Cl2 (0.72 mL). Purification by flash column chromatography (petrol/ethyl acetate, 3:1) afforded E32 as a white solid (98 mg, 0.18 mmol, 82%). mp 132-134 °C (CH2Cl2); Rf 0.33 (petrol/ethyl acetate, 3:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.25-8.18 (m, 2H), 8.10 (d, J = 8.9 Hz, 2H), 7.92 (d, J = 8.9 Hz, 2H), 7.26-7.19 (m, 2H), 5.58 (d, J = 0.9 Hz, 1H), 5.53 (br. s, 1H), 2.21 (d, J = 0.9 Hz, 3H), 1.47 (d, J = 14.9 Hz, 1H), 1.41 (d, J = 14.9 Hz, 1H), 1.22 (s, 3H), 1.14 (s, 3H), 0.93 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 169.4, 165.8 (d, J = 257.9 Hz), 160.9, 149.5, 148.3, 135.9 (d, J = 3.2 Hz), 131.7 (d, J = 9.5 Hz), 128.4, 123.5, 116.7 (d, J = 22.9 Hz), 98.5, 62.0, 56.6, 31.7, 31.6, 29.3, 28.6, 12.4; 19F NMR (377 MHz, CDCl3): δ (ppm) = -103.1 (tt, J = 8.6, 4.8 Hz); IR (ATR): ṽ (cm ^–1 ) = 2980, 2888, 1383, 1251, 1154, 1089, 955; HRMS (ESI ⁺ ) calcd. for C ₂₄ H ₃₁ FN ₅ O ₅ S ₂ ⁺ [M+H] ⁺ : 552.1745, found:552.1736. [00424] N-((4-Fluorophenyl)(isoxazol-3-ylamino)((2,4,4-trimethylpent an-2- yl)imino)-λ6-sulfaneylidene)-4-nitrobenzenesulfonamide (E33) Prepared according to General Procedure D using E23 (162 mg, 0.31 mmol, 1.00 equiv.), CH ₂ Cl ₂ (1.03 mL), MeOTf (37 µL, 0.33 mmol, 1.05 equiv.) and 3-aminoisoxazole (55 mg, 0.65 mmol, 2.10 equiv.). Purification by flash column chromatography (petrol/ethyl acetate, 3:1 to 2:1) afforded E33 as a white solid (158 mg, 0.29 mmol, 95%). mp 118-120 °C (CH2Cl2); R _f 0.50 (petrol/ethyl acetate, 2:1); 1H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.25-8.19 (m, 2H), 8.09 (d, J = 8.8 Hz, 2H), 8.05 (d, J = 1.7 Hz, 1H), 7.91 (d, J = 8.8 Hz, 2H), 7.25-7.19 (m, 2H), 6.01 (d, J = 1.6 Hz, 1H), 5.66 (s, 1H), 1.45 (d, J = 14.9 Hz, 1H), 1.40 (d, J = 14.9 Hz, 1H), 1.19 (s, 3H), 1.13 (s, 3H), 0.90 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 165.8 (d, J = 258.0 Hz), 160.3, 158.6, 149.6, 148.1, 135.7 (d, J = 3.2 Hz), 131.7 (d, J = 9.6 Hz), 128.3, 123.5, 116.7 (d, J = 22.9 Hz), 101.6, 62.0, 56.4, 31.6, 31.5, 29.1, 28.7; 19F NMR (377 MHz, CDCl3): δ (ppm) = -102.9 (tt, J = 8.1, 4.1 Hz); IR (ATR): ṽ (cm ^–1 ) = 1561, 1529, 1462, 1350, 1301, 1154, 1090, 1062, 977, 741; HRMS (ESI ⁺ ) calcd. for C23H29FN5O5S2 ⁺ [M+H] ⁺ : 538.1589, found: 538.1580. [00425] N-((4-Fluorophenyl)(pyridin-2-ylamino)((2,4,4-trimethylpenta n-2- yl)imino)-λ6-sulfaneylidene)-4-nitrobenzenesulfonamide (E34) Prepared according to General Procedure D using E23 (156 mg, 0.30 mmol, 1.00 equiv.), CH2Cl2 (1.0 mL), MeOTf (36 µL, 0.32 mmol, 1.05 equiv.) and a solution of 2-aminopyridine (59 mg, 0.63 mmol, 2.10 equiv) in CH2Cl2 (1.0 mL). Purification by flash column chromatography (petrol/ethyl acetate, 1:1) afforded E34 as a white solid (160 mg, 0.29 mmol, 98%). mp 128-130 °C (CH2Cl2); Rf 0.50 (petrol/ethyl acetate, 1:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.54-6.42 (br. s, 1H), 8.22-8.16 (m, 2H), 7.98 (d, J = 8.9 Hz, 2H), 7.92-7.82 (m, 3H), 7.39 (ddd, J = 8.2, 7.3, 2.0 Hz, 1H), 7.22-7.15 (m, 2H), 6.72 (ddd, J = 7.3, 5.1, 1.0 Hz, 1H), 6.62 (dt, J = 8.2, 1.0 Hz, 1H), 1.48 (s, 2H), 1.25 (s, 3H), 1.18 (s, 3H), 0.95 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 165.5 (d, J = 256.8 Hz), 157.3, 149.2, 149.1, 146.3, 138.2, 137.6 (d, J = 2.8 Hz), 131.4 (d, J = 9.5 Hz), 128.2, 123.3, 118.0, 117.0, 116.4 (d, J = 22.9 Hz), 61.6, 56.9, 31.7, 31.6, 29.4, 29.3; 19F NMR (377 MHz, CDCl3): δ (ppm) = -103.9 (tt, J = 8.2, 4.9 Hz); IR (ATR): ṽ (cm ^–1 ) = 1589, 1527, 1348, 1299, 1232, 1149, 1087, 1029, 1008, 732; HRMS (ESI ⁺ ) calcd. for C25H31FN5O4S2 ⁺ [M+H] ⁺ : 548.1796, found: 548.1793. [00426] N-(Amino(4-fluorophenyl)((2,4,4-trimethylpentan-2-yl)imino)- λ6- sulfaneylidene)-4-nitrobenzenesulfonamide (E35) An oven-dried 10 mL round-bottom flask containing E23 (167 mg, 0.32 mmol, 1.00 equiv.) were sealed and subjected to three N ₂ evacuation/refill cycles before anhydrous CH ₂ Cl ₂ (1.07 mL) was added. The solution was cooled to 0 °C before MeOTf (38 µL, 0.34 mmol, 1.05 equiv.) was added. The reaction was warmed to room temperature and was stirred for 30 min. Then the ammonia (0.64 mL, 2 M in ⁱ PrOH, 1.28 mmol, 4.00 equiv.) was added and the reaction was stirred at room temperature for another 30 min. The reaction was then concentrated under reduced pressure and crude product was purified by flash column chromatography (petrol/ethyl acetate, 3:1 to 1:1) to afford sulfondiimidamide E35 as a white solid (108 mg, 0.23 mmol, 72%). mp 93-95 °C (CH ₂ Cl ₂ ); R _f 0.33 (petrol/ethyl acetate, 2:1); 1H NMR (400 MHz, CDCl3): δ (ppm) =8.16 (d, J = 8.9 Hz, 2H), 8.03-7.98 (m, 2H), 7.94 (d, J = 8.9 Hz, 2H), 7.11-7.04 (m, 2H), 5.30 (br. s, 1H), 3.37 (br. s, 1H), 1.56 (d, J = 14.9 Hz, 1H), 1.44 (d, J = 14.9 Hz, 1H), 1.31 (s, 3H), 1.15 (s, 3H), 0.96 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 165.3 (d, J = 256.8 Hz), 149.5, 149.3, 137.4, 130.4 (d, J = 9.4 Hz), 128.0, 123.8, 116.2 (d, J = 22.7 Hz), 61.0, 56.4, 31.71, 31.70, 29.8, 28.9; 19F NMR (377 MHz, CDCl3): δ (ppm) = -104.4 (s); IR (ATR): ṽ (cm ^–1 ) = 1528, 1349, 1281, 1153, 1096, 1059, 991, 962; HRMS (ESI ⁺ ) calcd. for C20H27FN4O4S2Na ⁺ [M+Na] ⁺ : 493.1350, found: 493.1350. [00427] N-((4-Fluorophenyl)(1H-indol-1-yl)((2,4,4-trimethylpentan-2- yl)imino)-λ6- sulfaneylidene)-4-nitrobenzenesulfonamide (E36) Prepared according to General Procedure D using E23 (167 mg, 0.32 mmol, 1.00 equiv.), CH2Cl2 (1.07 mL), MeOTf (38 µL, 0.34 mmol, 1.05 equiv.) and a solution of indole (79 mg, 0.67 mmol, 2.10 equiv) in CH2Cl2 (1.1 mL). Purification by flash column chromatography (petrol/ethyl acetate, 3:1 to 1:1) afforded E36 as a yellow oil (128 mg, 0.22 mmol, 70%). Rf 0.61 (petrol/ethyl acetate, 1:1); 1H NMR (400 MHz, CDCl3): δ (ppm) =10.07 (d, J = 3.2 Hz, 1H), 8.10 (d, J = 3.1 Hz, 1H), 7.93- 7.86 (m, 4H), 7.65 (d, J = 8.8 Hz, 2H), 7.37 (dt, J = 8.3, 0.9 Hz, 1H), 7.10 (ddd, J = 8.3, 6.8, 1.4 Hz, 1H), 7.02-6.96 (m, 2H), 6.93-6.83 (m, 2H), 1.60 (d, J = 14.5 Hz, 1H), 1.53 (d, J = 14.5 Hz, 1H), 1.39 (s, 3H), 1.36 (s, 3H), 1.07 (s, 9H); 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 164.9 (d, J = 256.0 Hz), 149.04, 148.96, 138.2 (d, J = 2.3 Hz), 136.7, 132.3, 130.5 (d, J = 9.2 Hz), 127.3, 123.8, 123.3, 122.6, 122.1, 118.9, 116.2 (d, J = 22.8 Hz), 113.4, 112.8, 60.6, 58.0, 32.04, 31.96, 31.9, 31.7; 19F NMR (377 MHz, CDCl ₃ ): δ (ppm) = -105.3 (tt, J = 8.0, 5.0 Hz); IR (ATR): ṽ (cm ^–1 ) = 1528, 1349, 1287, 1214, 1146, 1086, 1028, 1003, 733; HRMS (ESI ⁺ ) calcd. for C ₂₈ H ₃₂ FN ₄ O ₄ S ₂ ⁺ [M+H] ⁺ : 571.1844, found: 571.1843. [00428] N-((4-Fluorophenyl)(2-oxooxazolidin-3-yl)((2,4,4-trimethylpe ntan-2- yl)imino)-λ6-sulfaneylidene)-4-nitrobenzenesulfonamide (E37) Prepared according to General Procedure D using E23 (156 mg, 0.30 mmol, 1.00 equiv.), CH ₂ Cl ₂ (1.00 mL), MeOTf (36 µL, 0.31 mmol, 1.05 equiv.) and 2-oxazolidinone (55 mg, 0.63 mmol, 2.10 equiv.). The reaction was stirred at room temperature for 1 h. Purification by flash column chromatography (petrol/ethyl acetate, 2:1 to 1:1) afforded E37 as a colourless oil (141 mg, 0.26 mmol, 87%). R _f 0.41 (petrol/ethyl acetate, 1:1); 1H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.20 (d, J = 9.0 Hz, 2H), 7.86 (d, J = 9.0 Hz, 2H), 7.85- 7.80 (m, 2H), 7.08-7.02 (m, 2H), 4.36-4.28 (m, 3H), 4.21-4.12 (m, 1H), 1.73 (d, J = 14.5 Hz, 1H), 1.65 (d, J = 14.5 Hz, 1H), 1.58 (s, 3H), 1.52 (s, 3H), 1.07 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 165.5 (d, J = 257.5 Hz), 151.9, 149.6, 148.8, 135.4 (d, J = 3.1 Hz), 131.0 (d, J = 9.7 Hz), 127.6, 124.0, 116.3 (d, J = 23.0 Hz), 62.2, 61.8, 57.0, 47.4, 31.9, 31.8, 31.7, 31.4; 19F NMR (377 MHz, CDCl3): δ (ppm) = -103.5 (tt, J = 8.0, 4.9 Hz); IR (ATR): ṽ (cm ^–1 ) = 1773, 1529, 1349, 1303, 1154, 1123, 1086, 1031, 1004, 837, 728, 647; HRMS (ESI ⁺ ) calcd. for C23H29FN4O6S2Na ⁺ [M+Na] ⁺ : 563.1405, found: 563.1406; [00429] The following two compounds were prepared according to General Procedure D using E23 (300 mg, 0.58 mmol, 1.00 equiv.), CH2Cl2 (1.9 mL), MeOTf (69 µL, 0.61 mmol, 1.05 equiv.) and (S)-(+)-2-pyrrolidinemethanol (123 mg, 1.22 mmol, 2.10 equiv.). The reaction was stirred at room temperature for 1 h. Purification by flash column chromatography (CH ₂ Cl ₂ /ethyl acetate, 3:1) afforded E38 as a white solid (132 mg, 0.24 mmol, 41%) and E39 as a white solid (133 mg, 0.24 mmol, 41%). [00430] N-((R)-(4-Fluorophenyl)((S)-2-(hydroxymethyl)pyrrolidin-1-yl )((2,4,4- trimethylpentan-2-yl)imino)-λ6-sulfaneylidene)-4-nitrobenze nesulfonamide (E38) [00431] N-((S)-(4-Fluorophenyl)((S)-2-(hydroxymethyl)pyrrolidin-1-yl )((2,4,4- trimethylpentan-2-yl)imino)-λ6-sulfaneylidene)-4-nitrobenze nesulfonamide (E39) Diastereoisomer 1 (Sulfur stereochemistry not known) mp 44-46 °C (CH2Cl2); Rf 0.53 (CH2Cl2/ethyl acetate, 3:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.15 (d, J = 8.9 Hz, 2H), 7.83-7.78 (m, 2H), 7.75 (d, J = 8.9 Hz, 2H), 7.07-7.02 (m, 2H), 4.38 (tt, J = 8.4, 3.8 Hz, 1H), 3.84-3.04 (br. s, 1H), 3.77 (dd, J = 11.0, 4.3 Hz, 1H), 3.58 (dd, J = 11.0, 5.3 Hz, 1H), 3.05 (dt, J = 10.0, 7.0 Hz, 1H), 2.75 (ddd, J = 10.0, 7.0, 5.1 Hz, 1H), 2.04-1.93 (m, 1H), 1.92-1.80 (m, 2H), 1.76-1.67 (m, 1H), 1.65 (d, J = 14.5 Hz, 1H), 1.57 (d, J = 14.5 Hz, 1H), 1.48 (s, 3H), 1.46 (s, 3H), 1.00 (s, 9H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 165.0 (d, J = 256.1 Hz), 149.4, 149.3, 136.8 (d, J = 3.1 Hz), 131.2 (d, J = 9.2 Hz), 127.4, 123.8, 116.2 (d, J = 22.6 Hz), 65.9, 62.8, 60.3, 57.7, 46.7, 32.2, 31.9, 31.8, 31.5, 28.9, 24.5; 19F NMR (377 MHz, CDCl ₃ ): δ (ppm) = -105.3 (tt, J = 8.5, 5.1 Hz); IR (ATR): ṽ (cm ^–1 ) = 1529, 1383, 1349, 1298, 1234, 1152, 1086, 1051, 969; HRMS (ESI ⁺ ) calcd. for C ₂₅ H ₃₆ FN ₄ O ₅ S ₂ ⁺ [M+H] ⁺ : 555.2106, found: 555.2097; [α]^^ ^ : -76.0° (c = 1.0, CHCl ₃ ). Diastereoisomer 2 (Sulfur stereochemistry not known) mp 117-120 °C (CH2Cl2); Rf 0.47 (CH2Cl2/ethyl acetate, 3:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.20 (d, J = 8.8 Hz, 2H), 7.87 (d, J = 8.8 Hz, 2H), 7.76- 7.71 (m, 2H), 7.07-7.01 (m, 2H), 4.30 (tt, J = 8.6, 4.5 Hz, 1H), 4.05-3.55 (br. s, 1H), 3.71 (dd, J = 10.9, 7.2 Hz, 1H), 3.62 (dd, J = 10.9, 4.6 Hz, 1H), 3.12-3.00 (m, 2H), 2.04-1.94 (m, 1H), 1.78 (dt, J = 12.0, 6.6 Hz, 1H), 1.72-1.63 (m, 2H), 1.58 (d, J = 14.5 Hz, 1H), 1.51 (s, 3H), 1.47 (s, 3H), 1.45-1.36 (m, 1H), 1.03 (s, 9H); 13C NMR (101 MHz, (CD3)2CO): δ (ppm) = 165.6 (d, J = 252.6 Hz), 150.8, 150.0, 136.8 (d, J = 3.1 Hz), 131.7 (d, J = 9.5 Hz), 128.2, 124.6, 116.5 (d, J = 23.0 Hz), 66.6, 65.8, 60.4, 58.2, 48.2, 32.4, 32.3, 32.0, 31.8, 29.0, 24.9 (note: for the gem-dimethyl carbons in the tert-octyl group, NC(CH3)2CH2C(CH3)3, 2 peaks were found instead of 1 due to the loss of symmetry caused by chiral sulfur atom); 19F NMR (377 MHz, (CD3)2CO): δ (ppm) = -108.4 (tt, J = 8.6, 5.1 Hz); IR (ATR): ṽ (cm ^–1 ) = 1589, 1529, 1489, 1350, 1299, 1265, 1230, 1152, 1087, 1047, 977; HRMS (ESI ⁺ ) calcd. for C25H36FN4O5S2 ⁺ [M+H] ⁺ : 555.2106, found: 555.2106; [α]^^ ^ : +37.5° (c = 1.0, CHCl3). [00432] 4-(4-fluoro-N-(4-nitrosulfonyl)phenylsulfondiimidoyl)morphol ine (E40a) To a solution of sulfondiimidamide E1 (4.50 g, 8.33 mmol, 1.00 equiv.) in CH2Cl2 (83.3 mL) in an oven-dried 250 mL round bottom flask, was added TFA (3.21 mL, 41.70 mmol, 5.00 equiv.) at room temperature. The mixture was stirred at room temperature for 15 min before being concentrated in vacuo and diluted with ethyl acetate (300 mL). Then the mixture was basified to pH 10-11 using 1 M aq. NaOH solution. The product was extracted with ethyl acetate (2 × 100 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The crude product was purified by flash column chromatography (petrol/ethyl acetate, 1:1 to 1:2) to afford sulfondiimidamide E40a as a white solid (3.39 g, 7.92 mmol, 95%). mp 64-66 °C (CH ₂ Cl ₂ ); R _f 0.50 (petrol/ethyl acetate, 1:2); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.24 (d, J = 9.0 Hz, 2H), 8.08 (d, J = 9.0 Hz, 2H), 7.98- 7.93 (m, 2H), 7.23-7.17 (m, 2H), 3.72 (t, J = 4.7 Hz, 4H), 3.28 (br. s, 1H), 3.15-3.02 (m, 4H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 165.9 (d, J = 257.8 Hz), 149.7, 149.3, 130.4 (d, J = 9.5 Hz), 129.3 (d, J = 3.2 Hz), 127.9, 124.1, 116.7 (d, J = 22.9 Hz), 66.2, 46.8; 19F NMR (377 MHz, CDCl ₃ ): δ (ppm) = -102.9 (tt, J = 8.0, 4.9 Hz); IR (ATR): ṽ (cm ^–1 ) = 1528, 1351, 1300, 1154, 1089, 1067, 1052, 920; HRMS (ESI ⁺ ) calcd. for C ₁₆ H ₁₈ FN ₄ O ₅ S ₂ ⁺ [M+H] ⁺ : 429.0697, found: 429.0695. [00433] 4-(4-fluoro-N-(4-nitrosulfonyl)phenylsulfondiimidoyl)morphol ine (E40b) [00434] To a solution of sulfondiimidamide P36 (222 mg, 0.38 mmol, 1.00 equiv.) in anhydrous THF (3.80 mL) in an oven-dried 25 mL round-bottom flask was added TBAF solution (0.42 mL, 1.0 M in THF, 0.42 mmol, 1.10 equiv.) at 0 °C. After being stirred at 0 °C for 10 min, the reaction mixture was quenched with sat. aq. NaCl solution (120 mL). The product was extracted with ethyl acetate (3 × 60 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography (CH2Cl2/ethyl acetate, 3:1 to 2:1) to afford sulfondiimidamide E40b as a white solid (158 mg, 0.37 mmol, 97%). mp 64-66 °C (CH2Cl2); R _f 0.50 (petrol/ethyl acetate, 1:2); 1H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.24 (d, J = 9.0 Hz, 2H), 8.08 (d, J = 9.0 Hz, 2H), 7.98- 7.93 (m, 2H), 7.23-7.17 (m, 2H), 3.72 (t, J = 4.7 Hz, 4H), 3.28 (br. s, 1H), 3.15-3.02 (m, 4H); 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 165.9 (d, J = 257.8 Hz), 149.7, 149.3, 130.4 (d, J = 9.5 Hz), 129.3 (d, J = 3.2 Hz), 127.9, 124.1, 116.7 (d, J = 22.9 Hz), 66.2, 46.8; 19F NMR (377 MHz, CDCl ₃ ): δ (ppm) = -102.9 (tt, J = 8.0, 4.9 Hz); IR (ATR): ṽ (cm ^–1 ) = 1528, 1351, 1300, 1154, 1089, 1067, 1052, 920; HRMS (ESI ⁺ ) calcd. for C ₁₆ H ₁₈ FN ₄ O ₅ S ₂ ⁺ [M+H] ⁺ : 429.0697, found: 429.0695. [00435] 4-(4-fluoro-N-cyano-N-(4-nitrosulfonyl)phenylsulfondiimidoyl ) morpholine (E41) In an oven-dried 250 mL round bottom flask under nitrogen atmosphere, sulfondiimidamide E40 (3.05 g, 7.13 mmol, 1.00 equiv.) was dissolved in anhydrous MeCN (35.7 mL) at room temperature. Et3N (1.99 mL, 14.3 mmol, 2.00 equiv.) was then added, followed by the addition of a BrCN solution (2.14 mL, 5.0 M in MeCN, 10.7 mmol, 2.00 equiv.). After stirring at room temperature for 30 min, the reaction mixture was quenched with sat. aq. NaHCO3 solution (500 mL). The product was extracted with ethyl acetate (3 × 100 mL). The combined extracts were dried over anhydrous Na2SO4 and concentrated in vacuo. The crude product was purified by flash column chromatography (CH2Cl2/ethyl acetate, 8:1 to 4:1) to afford sulfondiimidamide E41 as a white solid (3.16 g, 6.98 mmol, 98%). mp 50-53 °C (CH2Cl2); Rf 0.58 (CH2Cl2/ethyl acetate, 4:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.38 (d, J = 8.9 Hz, 2H), 8.22 (d, J = 8.9 Hz, 2H), 8.05- 8.00 (m, 2H), 7.39-7.33 (m, 2H), 3.82 (t, J = 4.7 Hz, 4H), 3.40 (dt, J = 11.7, 4.6 Hz, 2H), 3.25 (dt, J = 11.7, 4.6 Hz, 2H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 167.1 (d, J = 262.0 Hz), 150.5, 147.3, 131.6 (d, J = 10.1 Hz), 128.7, 127.5 (d, J = 3.3 Hz), 124.6, 118.1 (d, J = 23.1 Hz), 109.3, 65.9, 46.7; 19F NMR (377 MHz, CDCl3): δ (ppm) = -98.3 (tt, J = 7.8, 4.8 Hz); IR (ATR): ṽ (cm ^–1 ) = 2360, 2208, 1530, 1350, 1166, 1107, 1084, 930, 846; HRMS (ESI ⁺ ) calcd. for C ₁₇ H ₁₆ FN ₅ O ₅ S ₂ Na ⁺ [M+Na] ⁺ : 476.0469, found: 476.0469. [00436] 4-(4-fluoro-N-cyano-phenylsulfondiimidoyl)morpholine (E42) In an oven-dried 50 mL round bottom flask, sulfondiimidamide E41 (650 mg, 1.43 mmol, 1.00 equiv.) was dissolved in anhydrous MeCN (14.3 mL) at room temperature. Then 1- dodecanethiol (860 µL, 3.58 mmol, 2.50 equiv.) was added, followed by the addition of DBU (536 µL, 3.58 mmol, 2.50 equiv.). After stirring at room temperature for 15 mins, the reaction was purified by flash column chromatography (CH ₂ Cl ₂ /ethyl acetate, 4:1 to 1:1 to 0:1) without concentration to afford sulfondiimidamide E42 as a colourless oil (278 mg, 1.04 mmol, 73%). R _f 0.38 (ethyl acetate); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.03-7.98 (m, 2H), 7.30-7.25 (m, 2H), 3.75 (dt, J = 5.0, 3.0 Hz, 4H), 3.12-3.03 (m, 5H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 166.1 (d, J = 258.1 Hz), 130.9 (d, J = 9.5 Hz), 128.6 (d, J = 3.1 Hz), 117.1 (d, J = 22.9 Hz), 113.0, 66.2, 46.8; 19F NMR (377 MHz, CDCl3): δ (ppm) = -102.5 (tt, J = 8.0, 4.9 Hz); IR (ATR): ṽ (cm ^–1 ) = 2186, 1588, 1490, 1226, 1109, 924, 839; HRMS (ESI ⁺ ) calcd. for C11H14FN4OS ⁺ [M+H] ⁺ : 269.0867, found: 269.0869. [00437] N-((4-Fluorophenyl)(2-oxooxazolidin-3-yl)((methylsulfonyl)im ino)-λ6- sulfaneylidene)-4-nitrobenzenesulfonamide (E43) In an oven-dried 25 mL round bottom flask under nitrogen atmosphere, sulfondiimidamide E40 (190 mg, 0.44 mmol, 1.00 equiv.) was dissolved in anhydrous CH ₂ Cl ₂ (2.2 mL) at room temperature. Et ₃ N (92 µL, 0.66 mmol, 1.50 equiv.) was then added, followed by the addition of MsCl (61 mg, 0.53 mmol, 1.20 equiv.) and DMAP (11 mg, 0.088 mmol, 0.20 equiv.). After stirring at room temperature for 30 min, the reaction mixture was quenched with sat. aq. NaCl solution (100 mL). The product was extracted with CH ₂ Cl ₂ (3 × 50 mL). The combined extracts were dried over anhydrous Na ₂ SO ₄ and concentrated in vacuo. The crude product was purified by flash column chromatography (CH ₂ Cl ₂ /ethyl acetate, 5:1) to afford sulfondiimidamide E43 as a white solid (181 mg, 0.36 mmol, 81%). mp 56-58 °C (CH2Cl2); Rf 0.47 (CH2Cl2/ethyl acetate, 5:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.23 (d, J = 8.9 Hz, 2H), 8.05 (d, J = 8.9 Hz, 2H), 7.96- 7.91 (m, 2H), 7.24-7.17 (m, 2H), 3.71 (ddd, J = 5.2, 3.9, 1.2 Hz, 4H), 3.25 (dt, J = 12.1, 4.8 Hz, 2H), 3.19 (dt, J = 11.0, 4.3 Hz, 2H), 3.15 (s, 3H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 166.5 (d, J = 260.3 Hz), 150.0, 147.6, 131.5 (d, J = 9.9 Hz), 129.5 (d, J = 3.1 Hz), 128.2, 124.1, 117.4 (d, J = 23.1 Hz), 65.9, 46.4, 44.0; 19F NMR (377 MHz, CDCl3): δ (ppm) = -100.2 (tt, J = 8.2, 4.7 Hz); IR (ATR): ṽ (cm ^–1 ) = 1530, 1351, 1307, 1169, 1084, 926, 741; HRMS (ESI ⁺ ) calcd. for C17H20FN4O7S3 ⁺ [M+H] ⁺ : 507.0473, found: 507.0470. [00438] N-((4-Fluorophenyl)(2-oxooxazolidin-3-yl)(imino)-λ6-sulfane ylidene)- methanesulfonamide (E44) In an oven-dried 25 mL round bottom flask, sulfondiimidamide E43 (152 mg, 0.30 mmol, 1.00 equiv.) was dissolved in anhydrous MeCN (3.0 mL) at room temperature. Then 1- dodecanethiol (360 µL, 1.50 mmol, 5.0 equiv.) was added, followed by the addition of DBU (213 µL, 1.43 mmol, 4.75 equiv.). After stirring at room temperature for 15 mins, the reaction mixture was quenched with sat. aq. NaCl solution (100 mL). The product was extracted with ethyl acetate (3 × 50 mL). The combined extracts were dried over anhydrous Na ₂ SO ₄ and concentrated in vacuo. The crude product was purified by flash column chromatography (ethyl acetate/MeOH, 1:0 to 9:1) to afford sulfondiimidamide E44 as a colourless oil (68 mg, 0.21 mmol, 71%). R _f 0.50 (ethyl acetate/MeOH, 9:1); 1H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 7.92-7.86 (m, 2H), 7.12-7.06 (m, 2H), 3.58 (ddd, J = 5.8, 3.8, 2.1 Hz, 4H), 3.15 (s, 1H), 3.01-2.94 (m, 2H), 2.94-2.85 (m, 5H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 165.7 (d, J = 257.0 Hz), 130.3 (d, J = 9.4 Hz), 129.9 (d, J = 3.1 Hz), 116.6 (d, J = 22.7 Hz), 66.3, 46.9, 44.6; 19F NMR (377 MHz, CDCl3): δ (ppm) = -103.7 (tt, J = 8.0, 5.1 Hz); IR (ATR): ṽ (cm ^–1 ) = 1590, 1490, 1292, 1137, 1092, 1051, 1009, 913, 725; HRMS (ESI ⁺ ) calcd. for C11H17FN3O3S2 ⁺ [M+H] ⁺ : 322.0690, found: 322.0685. [00439] N-((4-Fluorophenyl)(2-oxooxazolidin-3-yl)((4-nitrobenzoyl)im ino)-λ6- sulfaneylidene)-4-nitrobenzenesulfonamide (E45) In an oven-dried 25 mL round bottom flask under nitrogen atmosphere, sulfondiimidamide E40 (164 mg, 0.38 mmol, 1.00 equiv.) was dissolved in anhydrous CH2Cl2 (1.9 mL) at room temperature. Et3N (80 µL, 0.57 mmol, 1.50 equiv.) was then added, followed by the addition of 4-nitrobenzoyl chloride (78 mg, 0.42 mmol, 1.10 equiv.). After stirring at room temperature for 1 h, the reaction mixture was quenched with sat. aq. NaCl solution (100 mL). The product was extracted with CH2Cl2 (3 × 50 mL). The combined extracts were dried over anhydrous Na2SO4 and concentrated in vacuo. The crude product was purified by flash column chromatography (CH2Cl2/ethyl acetate, 7:1 to 4:1) to afford sulfondiimidamide E45 as a white solid (207 mg, 0.36 mmol, 94%). mp 222-224 °C (CH2Cl2); Rf 0.75 (CH2Cl2/ethyl acetate, 5:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.18 (d, J = 9.0 Hz, 2H), 8.14-8.09 (m, 2H), 8.04-7.97 (m, 4H), 7.94 (d, J = 9.0 Hz, 2H), 7.34-7.28 (m, 2H), 3.87-3.81 (m, 4H), 3.63-3.56 (m, 2H), 3.45-3.39 (m, 2H); 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) =169.1, 166.5 (d, J = 260.0 Hz), 150.5, 149.8, 147.4, 139.6, 131.6 (d, J = 9.9 Hz), 130.2, 129.8 (d, J = 3.2 Hz), 128.6, 123.9, 123.5, 117.6 (d, J = 23.0 Hz), 66.2, 46.2; 19F NMR (377 MHz, CDCl ₃ ): δ (ppm) = -100.4 (tt, J = 7.7, 4.9 Hz); IR (ATR): ṽ (cm ^–1 ) = 1525, 1349, 1272, 1107, 1083, 1066, 936, 839, 720; HRMS (ESI ⁺ ) calcd. for C ₂₃ H ₂₁ FN ₅ O ₈ S ₂ ⁺ [M+H] ⁺ : 578.0810, found: 578.0809. [00440] 4-(4-fluoro-N-(4-nitrobenzoyl)phenylsulfondiimidoyl)morpholi ne (E46) In an oven-dried 25 mL round bottom flask, sulfondiimidamide E45 (202 mg, 0.35 mmol, 1.00 equiv.) was dissolved in anhydrous MeCN (3.5 mL) at room temperature. Then 1- dodecanethiol (420 µL, 1.75 mmol, 5.00 equiv.) was added, followed by the addition of DBU (248 µL, 1.66 mmol, 4.75 equiv.). After stirring at room temperature for 30 min, the reaction mixture was quenched with sat. aq. NaCl solution (120 mL). The product was extracted with ethyl acetate (3 × 50 mL). The combined extracts were dried over anhydrous Na ₂ SO ₄ and concentrated in vacuo. The crude product was purified by flash column chromatography (CH2Cl2/ethyl acetate, 1:1 to 1:2) to afford sulfondiimidamide E46 as a colourless oil (94 mg, 0.24 mmol, 69%). Rf 0.39 (CH2Cl2/ethyl acetate, 1:2); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.25-8.16 (m, 4H), 8.13-8.08 (m, 2H), 7.27-7.21 (m, 2H), 3.69 (td, J = 4.8, 1.8 Hz, 4H), 3.50 (s, 1H), 3.13 (dt, J = 12.0, 4.8 Hz, 2H), 3.04 (dt, J = 12.0, 4.8 Hz, 2H); 13C NMR (101 MHz, (CD3)2CO): δ (ppm) = 171.4, 166.2 (d, J = 252.8 Hz), 150.8, 143.3, 132.2(d, J = 1.7 Hz), 131.5 (d, J = 9.5 Hz), 130.9, 124.0, 117.1 (d, J = 23.0 Hz), 66.9, 47.2; 19F NMR (377 MHz, CDCl3): δ (ppm) = -104.0 (tt, J = 8.0, 4.0 Hz); IR (ATR): ṽ (cm ^–1 ) = 1627, 1590, 1522, 1490, 1287, 1258, 1138, 1110, 918, 721; HRMS (ESI ⁺ ) calcd. for C ₁₇ H ₁₈ FN ₄ O ₄ S ⁺ [M+H] ⁺ : 393.1027, found: 393.1024. [00441] N-((4-Fluorophenyl)(2-oxooxazolidin-3-yl)(((3,5- bis(trifluoromethyl)phenyl)carbamoyl)imino)-λ6-sulfaneylide ne)-4- nitrobenzenesulfonamide (E47) In an oven-dried 25 mL round bottom flask under nitrogen atmosphere, sulfondiimidamide E40 (255 mg, 0.60 mmol, 1.00 equiv.) was dissolved in anhydrous MeCN (6.0 mL) at room temperature. DBU (134 µL, 0.90 mmol, 1.50 equiv.) was then added, followed by the addition of 3,5-bis(trifluoromethyl)phenyl isocyanate (230 mg, 0.90 mmol, 1.50 equiv.). After stirring at room temperature for 30 min, the reaction mixture was quenched with sat. aq. NaCl solution (120 mL). The product was extracted with ethyl acetate (3 × 50 mL). The combined organic layers were dried over anhydrous Na ₂ SO ₄ and concentrated in vacuo. The crude product was purified by flash column chromatography (petrol/ethyl acetate, 1:1 to 2:3) to afford sulfondiimidamide E47 as a white solid (322 mg, 0.47 mmol, 79%). mp 196-198 °C (CH2Cl2); Rf 0.39 (petrol/ethyl acetate, 1:1); 1H NMR (400 MHz, (CD3)2SO): δ (ppm) = 10.01 (s, 1H), 8.18-8.13 (m, 2H), 8.08 (br. s, 4H), 7.85 (br. s, 2H), 7.59-7.51 (m, 3H), 3.69 (t, J = 4.6 Hz, 4H), 3.29 (q, J = 4.3 Hz, 4H); 13C NMR (101 MHz, (CD3)2SO): δ (ppm) = 165.5 (d, J = 254.9 Hz), 154.2, 148.9, 147.5, 141.2, 131.9 (d, J = 10.1 Hz), 130.7 (q, J = 32.7 Hz), 130.1 (d, J = 2.8 Hz), 128.7, 123.8, 123.2 (q, J = 272.6 Hz), 117.2, 117.1 (d, J = 23.2 Hz), 114.7, 65.3, 45.6; 19F NMR (377 MHz, (CD3)2SO): δ (ppm) = -62.0 (s), -103.6 (tt, J = 9.0, 5.1 Hz); IR (ATR): ṽ (cm ^–1 ) =1665, 1533, 1277, 1224, 1161, 1132, 1085, 940; HRMS (ESI ⁺ ) calcd. for C25H20F7N5O6S2Na ⁺ [M+Na] ⁺ : 706.0635, found: 706.0629. [00442] 4-(4-fluoro-N-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)phe nyl sulfondiimidoyl)morpholine (E48) In an oven-dried 25 mL round bottom flask, sulfondiimidamide E47 (180 mg, 0.26 mmol, 1.00 equiv.) was dissolved in anhydrous MeCN (2.6 mL) at room temperature. Then 1- dodecanethiol (316 µL, 1.32 mmol, 5.00 equiv.) was added, followed by the addition of DBU (187 µL, 1.25 mmol, 4.75 equiv.). After stirring at 0 °C for 30 min, the reaction mixture was quenched with sat. aq. NaCl solution (120 mL). The product was extracted with ethyl acetate (3 × 50 mL). The combined extracts were dried over anhydrous Na2SO4 and concentrated in vacuo. The crude product was purified by flash column chromatography (petrol/ethyl acetate, 1:1 to 1:2) to afford sulfondiimidamide E48 as a colorless oil (95 mg, 0.19 mmol, 72%). Rf 0.50 (petrol/ethyl acetate, 1:2); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.07-8.02 (m, 2H), 7.93 (s, 2H), 7.67 (br. s, 1H), 7.46 (s, 1H), 7.24-7.18 (m, 2H), 3.71 (t, J = 4.7 Hz, 4H), 3.43 (s, 1H), 3.10 (dt, J = 11.7, 4.7 Hz, 2H), 3.03 (dt, J = 11.7, 4.7 Hz, 2H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 165.7 (d, J = 256.6 Hz), 158.2, 141.1, 132.2 (q, J = 33.1 Hz), 130.2 (d, J = 9.3 Hz), 130.0 (d, J = 2.8 Hz), 123.4 (q, J = 272.6 Hz), 118.5, 116.6 (d, J = 22.6 Hz), 115.8, 66.4, 46.6; 19F NMR (377 MHz, CDCl3): δ (ppm) = -63.0 (s), -104.3 (s); IR (ATR): ṽ (cm ^–1 ) = 1638, 1541, 1492, 1474, 1434, 1387, 1277, 1236, 1176, 1129, 924; HRMS (ESI ⁺ ) calcd. for C19H18F7N4O2S ⁺ [M+H] ⁺ : 499.1033, found: 499.1029. [00443] 4-(4-fluoro-N-cyano-N-phenyl-phenylsulfondiimidoyl)morpholin e (E49) Sulfondiimidamide E42 (83 mg, 0.31 mmol, 1.00 equiv.), phenylboronic acid (94 mg, 0.77 mmol, 2.50 equiv.), Cu(MeCN)4PF6 (58 mg, 0.16 mmol, 0.50 equiv.), N-methylpiperidine (277 mg, 2.79 mmol, 9.00 equiv.) were added to an oven-dried 25 mL vial and dissolved in anhydrous MeCN (3.1 mL) under oxygen atmosphere. The reaction was stirred at room temperature for 3 h until completion (TLC). The reaction mixture was quenched with sat. aq. NaCl solution (80 mL). The product was extracted with ethyl acetate (3 × 30 mL). The combined extracts were dried over anhydrous Na2SO4 and concentrated in vacuo. The crude product was purified by flash column chromatography (CH2Cl2/ethyl acetate, 8:1 to 4:1) to afford sulfondiimidamide E49 as a white solid (81 mg, 0.24 mmol, 76%). mp 107-109°C (CH2Cl2); Rf 0.58 (CH2Cl2/ethyl acetate, 4:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.07-8.02 (m, 2H), 7.32-7.22 (m, 6H), 7.07 (tt, J = 7.2, 1.5 Hz, 1H), 3.68 (ddd, J = 9.2, 5.5, 3.8 Hz, 4H), 3.14 (dt, J = 5.5, 3.7 Hz, 4H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 166.0 (d, J = 258.1 Hz), 140.6, 131.2 (d, J = 9.6 Hz), 129.5, 128.7 (d, J = 3.3 Hz), 124.1, 123.9, 117.2 (d, J = 22.9 Hz), 112.8, 66.0, 46.8; 19F NMR (377 MHz, CDCl3): δ (ppm) = -102.3 (tt, J = 8.0, 5.0 Hz); IR (ATR): ṽ (cm ^–1 ) = 2980, 2190, 1588, 1487, 1259, 1238, 1110, 927, 843, 759; HRMS (ESI ⁺ ) calcd. for C ₁₇ H ₁₈ FN ₄ OS ⁺ [M+H] ⁺ : 345.1180, found: 345.1181. [00444] 4-(4-fluoro-N-cyano-N-((trifluoromethyl)thio)-phenylsulfondi imidoyl) morpholine (E50) In an oven-dried 10 mL vial under nitrogen atmosphere, sulfondiimidamide E42 (170 mg, 0.63 mmol, 1.00 equiv.) was dissolved in anhydrous MeCN (1.26 mL) at room temperature. NBS (107 mg, 0.60 mmol, 0.95 equiv.) was then added and stirred at room temperature for 30 min, followed by the addition of a solution of AgSCF ₃ (158 mg, 0.76 mmol, 1.20 equiv.) in anhydrous MeCN (1.9 mL). After stirring at room temperature for an additional 30 min, the reaction mixture was purified by flash column chromatography (CH ₂ Cl ₂ /ethyl acetate, 50:1 to 20:1 to 10:1) to afford sulfondiimidamide E50 as a colourless oil (119 mg, 0.32 mmol, 51%). R _f 0.57 (CH ₂ Cl ₂ /ethyl acetate, 10:1); 1H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 7.99-7.94 (m, 2H), 7.35-7.29 (m, 2H), 3.76 (ddd, J = 5.3, 3.9, 1.4 Hz, 4H), 3.18 (ddd, J = 8.0, 5.5, 4.4 Hz, 4H); 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 166.5 (d, J = 260.3 Hz), 131.5 (d, J = 9.9 Hz), 130.0 (q, J = 312.0 Hz), 127.2 (d, J = 3.2 Hz), 117.7 (d, J = 23.0 Hz), 110.6, 65.9, 46.9; 19F NMR (377 MHz, CDCl3): δ (ppm) = -49.8 (s), -100.1 (tt, J = 7.8, 4.7 Hz); IR (ATR): ṽ (cm ^–1 ) =2200, 1586, 1490, 1159, 1108, 1085, 1007, 930, 841;. HRMS (ESI ⁺ ) calcd. for C12H13F4N4OS2 ⁺ [M+H] ⁺ : 369.0461, found: 369.0467. [00445] 4-(4-fluoro-N-cyano-N-(phenoxycarbonyl)-phenylsulfondiimidoy l) morpholine (E51) In an oven-dried 25 mL round bottom flask under nitrogen atmosphere, sulfondiimidamide E42 (132 mg, 0.49 mmol, 1.00 equiv.) was dissolved in anhydrous CH ₂ Cl ₂ (2.5 mL) at room temperature. Et ₃ N (136 µL, 0.98 mmol, 2.0 equiv.) was then added, followed by the addition of phenyl chloroformate (115 mg, 0.73 mmol, 1.50 equiv.) and DMAP (12 mg, 0.098 mmol, 0.20 equiv.). After stirring at room temperature for 10 mins, the reaction mixture was quenched with sat. aq. NaCl solution (100 mL). The product was extracted with CH ₂ Cl ₂ (3 × 40 mL). The combined extracts were dried over anhydrous Na ₂ SO ₄ and concentrated in vacuo. The crude product was purified by flash column chromatography (CH2Cl2/ethyl acetate, 8:1 to 4:1) to afford sulfondiimidamide E51 as a white solid (177 mg, 0.46 mmol, 93%). mp 132-134 °C (CH2Cl2); Rf 0.50 (CH2Cl2/ethyl acetate, 4:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.12-8.07 (m, 2H), 7.38-7.30 (m, 4H), 7.24-7.19 (m, 1H), 7.18-7.14 (m, 2H), 3.80 (t, J = 4.7 Hz, 4H), 3.39 (dt, J = 12.2, 5.0 Hz, 2H), 3.32 (dt, J = 12.8, 5.0 Hz, 2H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 166.5 (d, J = 260.3 Hz), 154.5, 151.1, 131.4 (d, J = 9.9 Hz), 129.3, 127.6 (d, J = 3.0 Hz), 125.8, 121.3, 117.6 (d, J = 23.1 Hz), 110.4, 65.8, 46.2; 19F NMR (377 MHz, CDCl ₃ ): δ (ppm) = -99.8 (tt, J = 7.9, 4.7 Hz); IR (ATR): ṽ (cm ^–1 ) = 2202, 1697, 1588, 1489, 1237, 1184, 1158, 1107, 928, 838, 728; HRMS (ESI ⁺ ) calcd. for C ₁₈ H ₁₈ FN ₄ O ₃ S ⁺ [M+H] ⁺ : 389.1078, found: 389.1078. [00446] 4-(4-fluoro-N-cyano-N-(benzyl)-phenylsulfondiimidoyl)morphol ine (E52) Sulfondiimidamide E42 (120 mg, 0.45 mmol, 1.00 equiv.) was added to an oven-dried 25 mL round bottom flask under nitrogen atmosphere and dissolved in anhydrous MeCN (4.5 mL) at room temperature. DBU (202 µL, 1.35 mmol, 3.00 equiv.) was then added, followed by the addition of BnBr (192 mg, 1.12 mmol, 2.50 equiv.). After stirring at room temperature for 2.5 h, the reaction mixture was quenched with sat. aq. NaCl solution (120 mL). The product was extracted with ethyl acetate (3 × 40 mL). The combined extracts were dried over anhydrous Na2SO4 and concentrated in vacuo. The crude product was purified by flash column chromatography (CH2Cl2/ethyl acetate, 9:1 to 4:1) to afford sulfondiimidamide E52 as a colorless oil (131 mg, 0.37 mmol, 81%). Rf 0.63 (CH2Cl2/ethyl acetate, 4:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 8.00-7.95 (m, 2H), 7.46-7.42 (m, 2H), 7.37-7.33 (m, 3H), 7.30-7.24 (m, 2H), 4.56 (d, J = 14.4 Hz, 1H), 4.38 (d, J = 14.4 Hz, 1H), 3.65 (ddd, J = 11.8, 6.3, 3.2 Hz, 2H), 3.57 (ddd, J = 11.8, 6.3, 3.2 Hz, 2H), 3.03 (ddd, J = 11.9, 6.5, 3.2 Hz, 2H), 2.93 (ddd, J = 11.9, 6.5, 3.2 Hz, 2H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 165.8 (d, J = 257.5 Hz), 139.4, 130.8 (d, J = 9.5 Hz), 128.7 (d, J = 3.2 Hz), 128.5, 127.8, 127.2, 116.9 (d, J = 22.7 Hz), 113.3, 65.9, 46.8, 46.3; 19F NMR (377 MHz, CDCl3): δ (ppm) = -102.9 (tt, J = 8.0, 4.9 Hz); IR (ATR): ṽ (cm ^–1 ) = 2187, 1586, 1489, 1185, 1110, 928, 838; HRMS (ESI ⁺ ) calcd. for C18H20FN4OS ⁺ [M+H] ⁺ : 359.1336, found: 359.1336. [00447] 4-(4-fluoro-N-cyano-N-(prop-2-yn-1-yl)-phenylsulfondiimidoyl ) morpholine (E53) Sulfondiimidamide E42 (55.1 mg, 0.20 mmol, 1.00 equiv.) was added to an oven-dried 10 mL vial under nitrogen atmosphere and dissolved in anhydrous MeCN (2.1 mL) at room temperature. DBU (92 µL, 0.62 mmol, 3.00 equiv.) was then added, followed by the addition of propargyl bromide solution (76 mg, 80% wt in toluene, 0.51 mmol, 2.50 equiv.). After stirring at room temperature for 16 h, the reaction mixture was quenched with sat. aq. NaCl solution (100 mL). The product was extracted with ethyl acetate (3 × 30 mL). The combined extracts were dried over anhydrous Na ₂ SO ₄ and concentrated in vacuo. The crude product was purified by flash column chromatography (CH ₂ Cl ₂ /ethyl acetate, 10:1 to 4:1) to afford sulfondiimidamide E53 as a white solid (48.5 mg, 0.16 mmol, 77%).mp 128-131 °C (CH ₂ Cl ₂ ); Rf 0.54 (CH2Cl2/ethyl acetate, 4:1); 1H NMR (400 MHz, CDCl3): δ (ppm) = 7.99-7.94 (m, 2H), 7.30-7.24 (m, 2H), 4.14 (dd, J = 17.4, 2.5 Hz, 1H), 4.02 (dd, J = 17.4, 2.5 Hz, 1H), 3.78-3.72 (m, 4H), 3.17 (dt, J = 11.9, 4.8 Hz, 2H), 3.07 (dt, J = 11.3, 4.2 Hz, 2H), 2.28 (t, J = 2.5 Hz, 1H); 13C NMR (101 MHz, CDCl3): δ (ppm) = 166.0 (d, J = 257.9 Hz), 131.0 (d, J = 9.6 Hz), 128.4 (d, J = 3.2 Hz), 117.1 (d, J = 22.8 Hz), 112.9, 81.2, 71.5, 66.1, 47.0, 31.8; 19F NMR (377 MHz, CDCl3): δ (ppm) = -102.5 (tt, J = 8.0, 4.9 Hz); IR (ATR): ṽ (cm ^–1 ) = 2190, 1586, 1489, 1260, 1188, 1110, 928; HRMS (ESI ⁺ ) calcd. for C14H16FN4OS ⁺ [M+H] ⁺ : 307.1023, found: 307.1021. [00448] N-((4-Fluorophenyl)(3-phenylureido)(2,4,4-trimethylpentan-2- yl)imino)- λ6-sulfaneylidene)-4-nitrobenzenesulfonamide (E54) Sulfondiimidamide E35 (86 mg, 0.18 mmol, 1.00 equiv.) and NaH (11 mg, 60 % dispersion in mineral oil, 0.28 mmol, 1.50 equiv.) were added to an oven-dried 25 mL round-bottom flask at room temperature and the flask was purged with nitrogen gas. Anhydrous THF (1.80 mL) was then added, and the reaction was stirred at room temperature for 15 min. Phenyl isocyanate (26 mg, 0.22 mmol, 1.20 equiv.) was then added and the reaction was stirred at room temperature for 30 min. The reaction was quenched with sat. aq. NaCl solution (50 mL). Ethyl acetate (30 mL) was added and the organic layers was separated. The aqueous layers was further extracted with ethyl acetate (2 × 30 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude product was then purified by flash column chromatography (petrol/ethyl acetate, 3:1) to afford E54 as a white solid (88 mg, 0.15 mmol, 82%). Rf 0.50 (petrol/ethyl acetate, 2:1). 1H NMR (400 MHz, DMSO-d6): δ (ppm) = 9.33 (s, 1H), 8.18-8.06 (m, 5H), 7.87 (d, J = 8.8 Hz, 2H), 7.48 (t, J = 8.7 Hz, 2H), 7.34-7.30 (m, 2H), 7.17 (t, J = 7.9 Hz, 2H), 6.91 (t, J = 7.3 Hz, 1H), 1.53 (d, J = 14.7 Hz, 1H), 1.48 (d, J = 14.7 Hz, 1H), 1.19 (s, 3H), 1.10 (s, 3H), 0.87 (s, 9H). 13C NMR (101 MHz, DMSO-d6): δ (ppm) = 164.7 (d, J = 253.2 Hz), 154.1, 148.8, 148.4, 139.7, 137.5 (d, J = 2.3 Hz), 131.2 (d, J = 9.8 Hz), 128.4, 128.1, 123.7, 122.0, 117.9, 116.3 (d, J = 23.0 Hz), 60.7, 54.6, 31.19, 31.15, 28.5, 28.3. 19F NMR (377 MHz, DMSO-d6): δ (ppm) = -105.79 (td, J = 8.7, 4.2 Hz). IR (ATR): ṽ (cm ^–1 ) = 1528, 1349, 1301, 1223, 1156, 1087, 1056, 840, 739. HRMS (ESI ⁺ ) calcd. for C27H33FN5O5S2 ⁺ [M+H] ⁺ : 590.1902; found: 590.1894. [00449] N-((4-Fluorophenyl)(2-phenylacetamido)(2,4,4-trimethylpentan -2- yl)imino)-λ6-sulfaneylidene)-4-nitrobenzenesulfonamide (E55) In an oven-dried 25 mL round bottom flask under nitrogen atmosphere, sulfondiimidamide E35 (180 mg, 0.38 mmol, 1.00 equiv.) was dissolved in anhydrous CH ₂ Cl ₂ (2.5 mL) at room temperature. Et3N (80 µL, 0.57 mmol, 1.50 equiv.) was then added, followed by the addition of phenylacetyl chloride (70 mg, 0.46 mmol, 1.20 equiv.). After stirring at room temperature for 30 min, the reaction mixture was quenched with sat. aq. NaCl solution (100 mL). The product was extracted with CH ₂ Cl ₂ (3 × 40 mL). The combined extracts were dried over anhydrous Na ₂ SO ₄ and concentrated in vacuo. The crude product was purified by flash column chromatography (petrol/ethyl acetate, 3:1 to 2:1) to afford sulfondiimidamide E55 as a white solid (158 mg, 0.27 mmol, 70%). mp 78-80 °C (CH ₂ Cl ₂ ) Rf 0.50 (petrol/ethyl acetate, 2:1). 1H NMR (400 MHz, CDCl ₃ ): δ (ppm) = 8.13 (d, J = 8.9 Hz, 2H), 7.95 (d, J = 8.9 Hz, 2H), 7.88- 7.83 (m, 2H), 7.59 (br. s, 1H), 7.23-7.16 (m, 3H), 7.12-7.06 (m, 4H), 3.42 (s, 2H), 1.56 (d, J = 15.0 Hz, 1H), 1.47 (d, J = 14.9 Hz, 1H), 1.36 (s, 3H), 1.13 (s, 3H), 0.93 (s, 9H). 13C NMR (101 MHz, CDCl ₃ ): δ (ppm) = 179.3, 165.9 (d, J = 258.7 Hz), 149.7, 148.8, 136.6 (d, J = 3.3 Hz), 134.8, 130.6 (d, J = 9.6 Hz), 129.5, 128.6, 128.2, 127.1, 123.9, 116.9 (d, J = 23.0 Hz), 62.9, 56.6, 47.2, 31.8, 31.6, 29.4, 29.2; 19F NMR (377 MHz, CDCl3): δ (ppm) = -102.12 (tt, J = 7.8, 4.5 Hz). IR (ATR): ṽ (cm ^–1 ) = 1529, 1349, 1304, 1234, 1157, 1086. HRMS (ESI ⁺ ) calcd. for C28H33FN4O5S2Na ⁺ [M+Na] ⁺ : 611.1769; found: 611.1768. [00450] All references, including publications, patent applications, and patents, cited herein are hereby incorporated by reference in their entirety and to the same extent as if each reference were individually and specifically indicated to be incorporated by reference and were set forth in its entirety herein (to the maximum extent permitted by law). [00451] All headings and sub-headings are used herein for convenience only and should not be construed as limiting the invention in any way. [00452] The use of any and all examples, or exemplary language (e.g., "such as") provided herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention unless otherwise paragraphed. No language in the specification should be construed as indicating any non-paragraphed element as essential to the practice of the invention. [00453] The citation and incorporation of patent documents herein is done for convenience only and does not reflect any view of the validity, patentability, and/or enforceability of such patent documents. [00454] This invention includes all modifications and equivalents of the subject matter recited in the paragraphs appended hereto as permitted by applicable law.

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