F. Hoffmann-La Roche AG, CH-4070 Basel, Switzerland Case: 37559 NEW HETEROCYCLIC COMPOUNDS Field of the Invention The present invention relates to organic compounds useful for therapy or prophylaxis in a mammal, and in particular to monoacylglycerol lipase (MAGL) inhibitors for the treatment or prophylaxis of diseases and disorders that are associated with MAGL, such as neuroinflammation, neurodegenerative diseases, pain, cancer, mental disorders, multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, traumatic brain injury, neurotoxicity, stroke, epilepsy, anxiety, migraine, depression, inflammatory bowel disease, symptoms associated with inflammatory bowel disease, gut motility, visceral pain, fibromyalgia, endometriosis, abdominal pain, abdominal pain associated with irritable bowel syndrome, asthma, COPD, visceral pain, and/or renal disease in a mammal. Background of the Invention Endocannabinoids (ECs) are signaling lipids that exert their biological actions by interacting with cannabinoid receptors (CBRs), CB1 and CB2. They modulate multiple physiological processes including neuroinflammation, neurodegeneration and tissue regeneration (Iannotti, F.A., et al., Progress in lipid research 2016, 62, 107-28.). In the brain, the main endocannabinoid, 2-arachidonoylglycerol (2-AG), is produced by diacyglycerol lipases (DAGL) and hydrolyzed by the monoacylglycerol lipase, MAGL. MAGL hydrolyses 85% of 2-AG; the remaining 15% being hydrolysed by ABHD6 and ABDH12 (Nomura, D.K., et al., Science 2011, 334, 809.). MAGL is expressed throughout the brain and in most brain cell types, including neurons, astrocytes, oligodendrocytes and microglia cells (Chanda, P.K., et al., Molecular pharmacology 2010, 78, 996; Viader, A., et al., Cell reports 2015, 12, 798.).2-AG hydrolysis results in the formation of arachidonic acid (AA), the precursor of prostaglandins (PGs) and leukotrienes (LTs). Oxidative metabolism of AA is increased in inflamed tissues. There are two principal enzyme pathways of arachidonic acid oxygenation involved in inflammatory processes, CNE/18.07.2023 the cyclo-oxygenase which produces PGs and the 5-lipoxygenase which produces LTs. Of the various cyclooxygenase products formed during inflammation, PGE2 is one of the most important. These products have been detected at sites of inflammation, e.g. in the cerebrospinal fluid of patients suffering from neurodegenerative disorders and are believed to contribute to inflammatory response and disease progression. Mice lacking MAGL (Mgll-/-) exhibit dramatically reduced 2-AG hydrolase activity and elevated 2-AG levels in the nervous system while other arachidonoyl-containing phospho- and neutral lipid species including anandamide (AEA), as well as other free fatty acids, are unaltered. Conversely, levels of AA and AA-derived prostaglandins and other eicosanoids, including prostaglandin E2 (PGE2), D2 (PGD2), F2 (PGF2), and thromboxane B2 (TXB2), are strongly decreased. Phospholipase A2 (PLA2) enzymes have been viewed as the principal source of AA, but cPLA ₂ -deficient mice have unaltered AA levels in their brain, reinforcing the key role of MAGL in the brain for AA production and regulation of the brain inflammatory process. Neuroinflammation is a common pathological change characteristic of diseases of the brain including, but not restricted to, neurodegenerative diseases (e.g. multiple sclerosis, Alzheimer’s disease, Parkinson disease, amyotrophic lateral sclerosis, traumatic brain injury, neurotoxicity, stroke, epilepsy and mental disorders such as anxiety and migraine). In the brain, production of eicosanoids and prostaglandins controls the neuroinflammation process. The pro-inflammatory agent lipopolysaccharide (LPS) produces a robust, time-dependent increase in brain eicosanoids that is markedly blunted in Mgll–/– mice. LPS treatment also induces a widespread elevation in pro-inflammatory cytokines including interleukin-1-a (IL-1-a), IL-1b, IL-6, and tumor necrosis factor-a (TNF-a) that is prevented in Mgll–/– mice. Neuroinflammation is characterized by the activation of the innate immune cells of the central nervous system, the microglia and the astrocytes. It has been reported that anti-inflammatory drugs can suppress in preclinical models the activation of glia cells and the progression of disease including Alzheimer’s disease and mutiple sclerosis (Lleo A., Cell Mol Life Sci.2007, 64, 1403.). Importantly, genetic and/or pharmacological disruption of MAGL activity also blocks LPS-induced activation of microglial cells in the brain (Nomura, D.K., et al., Science 2011, 334, 809.). In addition, genetic and/or pharmacological disruption of MAGL activity was shown to be protective in several animal models of neurodegeneration including, but not restricted to, Alzheimer’s disease, Parkinson’s disease and multiple sclerosis. For example, an irreversible MAGL inhibitor has been widely used in preclinical models of neuroinflammation and neurodegeneration (Long, J.Z., et al., Nature chemical biology 2009, 5, 37.). Systemic injection of such inhibitor recapitulates the Mgll-/- mice phenotype in the brain, including an increase in 2-AG levels, a reduction in AA levels and related eicosanoids production, as well as the prevention of cytokines production and microglia activation following LPS-induced neuroinflammation (Nomura, D.K., et al., Science 2011, 334, 809.), altogether confirming that MAGL is a druggable target. Consecutive to the genetic and/or pharmacological disruption of MAGL activity, the endogenous levels of the MAGL natural substrate in the brain, 2-AG, are increased.2-AG has been reported to show beneficial effects on pain with, for example, anti-nociceptive effects in mice (Ignatowska-Jankowska B. et al., J. Pharmacol. Exp. Ther.2015, 353, 424.) and on mental disorders, such as depression in chronic stress models (Zhong P. et al., Neuropsychopharmacology 2014, 39, 1763.). Furthermore, oligodendrocytes (OLs), the myelinating cells of the central nervous system, and their precursors (OPCs) express the cannabinoid receptor 2 (CB2) on their membrane.2-AG is the endogenous ligand of CB1 and CB2 receptors. It has been reported that both cannabinoids and pharmacological inhibition of MAGL attenuate OLs’s and OPCs’s vulnerability to excitotoxic insults and therefore may be neuroprotective (Bernal-Chico, A., et al., Glia 2015, 63, 163.). Additionally, pharmacological inhibition of MAGL increases the number of myelinating OLs in the brain of mice, suggesting that MAGL inhibition may promote differentiation of OPCs in myelinating OLs in vivo (Alpar, A., et al., Nature communications 2014, 5, 4421.). Inhibition of MAGL was also shown to promote remyelination and functional recovery in a mouse model of progressive multiple sclerosis (Feliu A. et al., Journal of Neuroscience 2017, 37 (35), 8385.). In recent years, metabolism is talked highly important in cancer research, especially the lipid metabolism. Researchers believe that the de novo fatty acid synthesis plays an important role in tumor development. Many studies illustrated that endocannabinoids have anti-tumorigenic actions, including anti-proliferation, apoptosis induction and anti-metastatic effects. MAGL as an important decomposing enzyme for both lipid metabolism and the endocannabinoids system, additionally as a part of a gene expression signature, contributes to different aspects of tumourigenesis (Qin, H., et al., Cell Biochem. Biophys.2014, 70, 33; Nomura DK et al., Cell 2009, 140(1), 49-61; Nomura DK et al., Chem. Biol.2011, 18(7), 846-856; Jinlong Yin et al, Nature Communications 2020, 11, 2978). The endocannabinoid system is also invlolved in many gastrointestinal physiological and physiopathological actions (Marquez, Suarez et al.2009). All these effects are driven mainly via cannabinoid receptors (CBRs), CB1 and CB2. CB1 receptors are present throughout the GI tract of animals and healthy humans, especially in the enteric nervous system (ENS) and the epithelial lining, as well as smooth muscle cells of blood vessels in the colonic wall (Wright, Rooney et al. 2005), (Duncan, Davison et al.2005). Activation of CB1 produces anti-emetic, anti-motility, and anti-inflammatory effect, and help to modulate pain (Perisetti, Rimu et al.2020). CB2 receptors are expressed in immune cells such as plasma cells and macrophages, in the lamina propria of the GI tract (Wright, Rooney et al.2005), and primarily on the epithelium of human colonic tissue associated with inflammatory bowel disease (IBD). Activation of CB2 exerts anti- inflammatory effect by reducing pro-inflammatory cytokines. Expression of MAGL is increased in colonic tissue in UC patients (Marquez, Suarez et al.2009) and 2-AG levels are increased in plasma of IBD patients (Grill, Hogenauer et al.2019). Several animal studies have demonstrated the potential of MAGL inhibitors for symptomatic treatment of IBD. MAGL inhibition prevents TNBS-induced mouse colitis and decreases local and circulating inflammatory markers via a CB1/CB2 MoA (Marquez, Suarez et al.2009). Furthermore, MAGL inhibition improves gut wall integrity and intestinal permeability via a CB1 driven MoA (Wang, Zhang et al.2020). In conclusion, suppressing the action and/or the activation of MAGL is a promising new therapeutic strategy for the treatment or prevention of various diseases and disorders. WO2020104494 discloses certain MAGL inhibitors. However, it was found that, while those MAGL inhibitors have properties that make them particularly suitable for the treatment of CNS indications, such as multiple sclerosis, some properties (e.g. high permeability) means that they are less suitable if a differential exposure across tissues is required. This could make them less suitable for the treatment of certain disorders, which may benefit from achieving higher exposure in target tissues than in the rest of the body. Accordingly, there continues to be a high unmet medical need for new MAGL inhibitors, especially for new MAGL inhibitors with distinct properties such that different exposures can be achieved in different tissues. Summary of the Invention Surprisingly, starting from the compounds disclosed in WO2020104494, a number of chemical modifications enabled a marked reduction in passive permeability (P _app ), while maintaining high cellular potency and excellent overall drug-like properties. The compounds of the present invention were found to be particularly useful for indications benefitting from differential levels of MAGL inhibition in different tissues, in particular indications benefitting from a higher level of MAGL inhibition in the periphery than in the brain. In a first aspect, the present invention provides a compound of formula (I) wherein A, B, R ¹ , R ² , R ⁴ , and R ⁵ are as described herein. In one aspect, the present invention provides a process of manufacturing a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, comprising: (a) reacting an amine of formula 1b, wherein R ¹ , R ² , R ⁴ , R ⁵ , A and B are as described herein, with 6-(1,2,4-triazole-1-carbonyl)-4,4a,5,7,8,8a-hexahydropyrido[ 4,3-b][1,4]oxazin- 3-one (2), 2 in the presence of a base; or (b) reacting 4a,5,6,7,8,8a-hexahydro-4H-pyrido[4,3-b][1,4]oxazin-3-one (2b) with a compound of formula 1c, wherein R ¹ , R ² , R ⁴ , R ⁵ , A and B are as described herein, in the presence of a base, to form said compound of formula (I). In a further aspect, the present invention provides a compound of formula (I) as described herein, when manufactured according to the processes described herein. In a further aspect, the present invention provides a compound of formula (I) as described herein, for use as therapeutically active substance. In a further aspect, the present invention provides a pharmaceutical composition comprising a compound of formula (I) as described herein and a therapeutically inert carrier. In a further aspect, the present invention provides a compound of formula (I) as described herein for use in the treatment or prophylaxis of diseases and disorders that are associated with MAGL. Detailed Description of the Invention Definitions Features, integers, characteristics, compounds, chemical moieties or groups described in conjunction with a particular aspect, embodiment or example of the invention are to be understood to be applicable to any other aspect, embodiment or example described herein, unless incompatible therewith. All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and/or steps are mutually exclusive. The invention is not restricted to the details of any foregoing embodiments. The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed. The term “alkyl” refers to a mono- or multivalent, e.g., a mono- or bivalent, linear or branched saturated hydrocarbon group of 1 to 6 carbon atoms (“C ₁ -C ₆ -alkyl”), e.g., 1, 2, 3, 4, 5, or 6 carbon atoms. In some embodiments, the alkyl group contains 1 to 3 carbon atoms, e.g., 1, 2 or 3 carbon atoms. Some non-limiting examples of alkyl include methyl, ethyl, propyl, 2-propyl (isopropyl), n-butyl, iso-butyl, sec-butyl, tert-butyl, and 2,2-dimethylpropyl. A particularly preferred, yet non-limiting example of alkyl is methyl. The term “alkoxy” refers to an alkyl group, as previously defined, attached to the parent molecular moiety via an oxygen atom. Unless otherwise specified, the alkoxy group contains 1 to 6 carbon atoms (“C1-C6-alkoxy”). In some preferred embodiments, the alkoxy group contains contains 1 to 4 carbon atoms. In still other embodiments, the alkoxy group contains 1 to 3 carbon atoms. Some non-limiting examples of alkoxy groups include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy and tert-butoxy. A particularly preferred, yet non-limiting example of alkoxy is methoxy. The term “halogen” or “halo” refers to fluoro (F), chloro (Cl), bromo (Br), or iodo (I). Preferably, the term “halogen” or “halo” refers to fluoro (F), chloro (Cl) or bromo (Br). Particularly preferred, yet non-limiting examples of “halogen” or “halo” are fluoro (F) and chloro (Cl). The term “cycloalkyl” as used herein refers to a saturated or partly unsaturated monocyclic hydrocarbon group of 3 to 10 ring carbon atoms (“C3-10-cycloalkyl”). In some preferred embodiments, the cycloalkyl group is a saturated monocyclic hydrocarbon group of 3 to 8 ring carbon atoms. Preferably, the cycloalkyl group is a saturated monocyclic hydrocarbon group of 3 to 6 ring carbon atoms, e.g., of 3, 4, 5 or 6 carbon atoms. Some non-limiting examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. A preferred, yet non-limiting example of cycloalkyl is cyclopropyl. The term “heterocyclyl” as used herein refers to a saturated or partly unsaturated monocyclic ring system of 3 to 6 ring atoms, wherein 1, 2, or 3 of said ring atoms are heteroatoms selected from N, O and S, the remaining ring atoms being carbon. Preferably, 1 to 2 of said ring atoms are selected from N and O, the remaining ring atoms being carbon. Some non-limiting examples of heterocyclyl groups include azetidine, pyrrolidine, piperidine, piperazinyl, and morpholine. A preferred, yet non-limiting example of heterocyclyl is azetidine. The term “cyano” refers to a –CN (nitrile) group. The term “oxo” refers to an oxygen atom bound to the parent molecule through a double bond (=O). The term “haloalkyl” refers to an alkyl group, wherein at least one of the hydrogen atoms of the alkyl group has been replaced by a halogen atom, preferably fluoro. Preferably, “haloalkyl” refers to an alkyl group wherein 1, 2 or 3 hydrogen atoms of the alkyl group have been replaced by a halogen atom, most preferably fluoro. A particularly preferred, yet non-limiting example of haloalkyl is trifluoromethyl (CF ₃ ). The term “haloalkylcycloalkyl” refers to a cycloalkyl group, wherein at least one of the hydrogen atoms of the cycloalkyl group has been replaced by a haloalkyl group, preferably by CF3. Preferably, “haloalkylcycloalkyl” refers to a cycloalkyl group wherein 1, 2 or 3 hydrogen atoms, in particular 1 hydrogen atom, of the cycloalkyl group have been replaced by a haloalkyl group, most preferably CF3. A particularly preferred, yet non-limiting example of haloalkylcycloalkyl is trifluoromethylcyclopropyl. The term “haloalkylheterocyclyl” refers to a heterocyclyl group, wherein at least one of the hydrogen atoms of the heterocyclyl group has been replaced by a haloalkyl group, preferably by CF3. Preferably, “haloalkylheterocyclyl” refers to a heterocyclyl group wherein 1, 2 or 3 hydrogen atoms, in particular 1 hydrogen atom, of the heterocyclyl group have been replaced by a haloalkyl group, most preferably CF ₃ . A particularly preferred, yet non-limiting example of haloalkylheterocyclyl is 3-(trifluoromethyl)azetidine. The term “haloalkoxy” refers to an alkoxy group, wherein at least one of the hydrogen atoms of the alkoxy group has been replaced by a halogen atom, preferably fluoro. Preferably, “haloalkoxy” refers to an alkoxy group wherein 1, 2 or 3 hydrogen atoms of the alkoxy group have been replaced by a halogen atom, most preferably fluoro. A particularly preferred, yet non- limiting example of haloalkoxy is trifluoromethoxy (–OCF3). The term "pharmaceutically acceptable salt" refers to those salts which retain the biological effectiveness and properties of the free bases or free acids, which are not biologically or otherwise undesirable. The salts are formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like, in particular hydrochloric acid, and organic acids such as acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p- toluenesulfonic acid, salicylic acid, N-acetylcystein and the like. In addition, these salts may be prepared by addition of an inorganic base or an organic base to the free acid. Salts derived from an inorganic base include, but are not limited to, the sodium, potassium, lithium, ammonium, calcium, magnesium salts and the like. Salts derived from organic bases include, but are not limited to salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, lysine, arginine, N-ethylpiperidine, piperidine, polyimine resins and the like. Particular pharmaceutically acceptable salts of compounds of formula (I) are hydrochloride salts. The term “protective group” (PG) denotes the group which selectively blocks a reactive site in a multifunctional compound such that a chemical reaction can be carried out selectively at another unprotected reactive site in the meaning conventionally associated with it in synthetic chemistry. Protective groups can be removed at the appropriate point. Exemplary protective groups are amino-protective groups, carboxy-protective groups or hydroxy-protective groups. Particular protective groups are the tert-butoxycarbonyl (Boc), benzyloxycarbonyl (Cbz), fluorenylmethoxycarbonyl (Fmoc) and benzyl (Bn). Further particular protective groups are the tert-butoxycarbonyl (Boc) and the fluorenylmethoxycarbonyl (Fmoc). More particular protective group is the tert-butoxycarbonyl (Boc). Exemplary protective groups and their application in organic synthesis are described, for example, in “Protective Groups in Organic Chemistry” by T. W. Greene and P. G. M. Wutts, 5th Ed., 2014, John Wiley & Sons, N.Y. The compounds of formula (I) can contain several asymmetric centers and can be present in the form of optically pure enantiomers, mixtures of enantiomers such as, for example, racemates, optically pure diastereioisomers, mixtures of diastereoisomers, diastereoisomeric racemates or mixtures of diastereoisomeric racemates. In a preferred embodiment, the compound of formula (I) according to the invention is a cis-enantiomer of formula (Ia) or (Ib), respectively, as described herein. According to the Cahn-Ingold-Prelog Convention, the asymmetric carbon atom can be of the "R" or "S" configuration. The abbreviation “MAGL” refers to the enzyme monoacylglycerol lipase. The terms “MAGL” and “monoacylglycerol lipase” are used herein interchangeably. The term “treatment” as used herein includes: (1) inhibiting the state, disorder or condition (e.g. arresting, reducing or delaying the development of the disease, or a relapse thereof in case of maintenance treatment, of at least one clinical or subclinical symptom thereof); and/or (2) relieving the condition (i.e., causing regression of the state, disorder or condition or at least one of its clinical or subclinical symptoms). The benefit to a patient to be treated is either statistically significant or at least perceptible to the patient or to the physician. However, it will be appreciated that when a medicament is administered to a patient to treat a disease, the outcome may not always be effective treatment. The term “prophylaxis” as used herein includes: preventing or delaying the appearance of clinical symptoms of the state, disorder or condition developing in a mammal and especially a human that may be afflicted with or predisposed to the state, disorder or condition but does not yet experience or display clinical or subclinical symptoms of the state, disorder or condition. The term “neuroinflammation” as used herein relates to acute and chronic inflammation of the nervous tissue, which is the main tissue component of the two parts of the nervous system; the brain and spinal cord of the central nervous system (CNS), and the branching peripheral nerves of the peripheral nervous system (PNS). Chronic neuroinflammation is associated with neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and multiple sclerosis. Acute neuroinflammation usually follows injury to the central nervous system immediately, e.g., as a result of traumatic brain injury (TBI). The term “traumatic brain injury” (“TBI”, also known as “intracranial injury”), relates to damage to the brain resulting from external mechanical force, such as rapid acceleration or deceleration, impact, blast waves, or penetration by a projectile. The term “neurodegenerative diseases” relates to diseases that are related to the progressive loss of structure or function of neurons, including death of neurons. Examples of neurodegenerative diseases include, but are not limited to, multiple sclerosis, Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. The term “mental disorders” (also called mental illnesses or psychiatric disorders) relates to behavioral or mental patterns that may cause suffering or a poor ability to function in life. Such features may be persistent, relapsing and remitting, or occur as a single episode. Examples of mental disorders include, but are not limited to, anxiety and depression. The term “pain” relates to an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Examples of pain include, but are not limited to, nociceptive pain, chronic pain (including idiopathic pain), neuropathic pain including chemotherapy induced neuropathy, phantom pain and phsychogenic pain. A particular example of pain is neuropathic pain, which is caused by damage or disease affecting any part of the nervous system involved in bodily feelings (i.e., the somatosensory system). In one embodiment, “pain” is neuropathic pain resulting from amputation or thoracotomy. In one embodiment, “pain” is chemotherapy induced neuropathy. The term “neurotoxicity” relates to toxicity in the nervous system. It occurs when exposure to natural or artificial toxic substances (neurotoxins) alter the normal activity of the nervous system in such a way as to cause damage to nervous tissue. Examples of neurotoxicity include, but are not limited to, neurotoxicity resulting from exposure to substances used in chemotherapy, radiation treatment, drug therapies, drug abuse, and organ transplants, as well as exposure to heavy metals, certain foods and food additives, pesticides, industrial and/or cleaning solvents, cosmetics, and some naturally occurring substances. The term “cancer” refers to a disease characterized by the presence of a neoplasm or tumor resulting from abnormal uncontrolled growth of cells (such cells being "cancer cells"). As used herein, the term cancer explicitly includes, but is not limited to, hepatocellular carcinoma, colon carcinogenesis and ovarian cancer. The term “mammal” as used herein includes both humans and non-humans and includes but is not limited to humans, non-human primates, canines, felines, murines, bovines, equines, and porcines. In a particularly preferred embodiment, the term “mammal” refers to humans. Compounds of the Invention In a first aspect, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein: (i) A is selected from 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,2,4- triazolyl, triazolyl, thiazolyl, imidazolyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, oxazolyl, 1,2-dihydropyridyl, [1,2,4]triazolo[4,3-a]pyridine, [1,2,4]triazolo[1,5-a]pyridine, 1H-pyrrolo[2,3-b]pyridine, imidazo[1,5- a]pyridine, imidazo[1,2-a]pyridine, 2H-pyrazolo[3,4-b]pyridine, 2H- pyrazolo[4,3-b]pyridine, 2H-pyrazolo[4,3-c]pyridine, pyrazolo[1,5- a]pyrimidine, 2H-pyrazolo[3,4-d]pyrimidine, [1,2,4]triazolo[1,5-a]pyrimidine, imidazo[1,2-a]pyrazine, 1,2-benzoxazole, 1H-indazole, 1H-imidazo[1,2- c]pyrimidin-5-one, 1H-pyrrolo[2,3-b]pyridine, imidazo[1,2-a]pyrimidine, 2H- pyrazolo[3,4-c]pyridine, 7H-pyrrolo[2,3-d]pyrimidine, [1,2,4]triazolo[1,5- b]pyrimidine, pyrazolo[1,5-a]pyrimidine, 2H-pyrazolo[4,3-b]pyridine, 1H- imidazo[4,5-b]pyridine, 3H-imidazo[4,5-b]pyridine, 4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine, 1H-pyrazolo[3,4-b]pyridine, 1H- imidazo[1,2-a]pyrimidin-5-one, and 2H-indazole; R ¹ is selected from halogen, C _1-6 -alkyl, C _1-6 -alkoxy, halo-C _1-6 -alkyl, hydroxy-C _1-6 - alkyl, C3-6-cycloalkyl-, halo-C1-6-alkyl-C3-6-cycloalkyl-, (halo-C1-6-alkyl)-(3- to 6-membered heterocyclyl)-, halo-C _1-6 -alkoxy, (C _1-6 -alkyl) ₂ PO-, and a group R ² is selected from hydrogen, halogen, cyano, oxo, C1-6-alkyl and halo-C1-6-alkyl; R ³ is selected from C1-6-alkyl, halo-C1-6-alkyl, and 4- to 6-membered heterocyclyl, wherein said 4- to 6-membered heterocyclyl is optionally substituted with a halo-C1-6-alkyl substituent; X is selected from O and NH; or (ii) A is pyridyl; R ¹ is selected from halogen, C _1-6 -alkyl, C _1-6 -alkoxy, halo-C _1-6 -alkyl, hydroxy-C _1-6 - alkyl, C3-6-cycloalkyl-, halo-C1-6-alkyl-C3-6-cycloalkyl-, halo-C1-6-alkoxy, (C1- 6-alkyl) ₂ PO-, and a group R ² is selected from hydrogen, halogen, cyano, C _1-6 -alkyl and halo-C _1-6 -alkyl; R ³ is selected from C _1-6 -alkyl, halo-C _1-6 -alkyl, and 4- to 6-membered heterocyclyl, wherein said 4- to 6-membered heterocyclyl is optionally substituted with a halo-C1-6-alkyl substituent; and X is selected from O and NH; or (iii) A is phenyl; R ¹ is selected from (C -alkyl) 1-6 2PO- and a group ; R ² is selected from hydrogen, halogen, cyano, C1-6-alkyl and halo-C1-6-alkyl; R ³ is selected from C _1-6 -alkyl, halo-C _1-6 -alkyl, and 4- to 6-membered heterocyclyl, wherein said 4- to 6-membered heterocyclyl is optionally substituted with a halo-C1-6-alkyl substituent; and X is selected from O and NH; R ⁴ and R ⁵ are each independently selected from hydrogen, halogen and C _1-6 -alkyl; and B is selected from: In a further aspect, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: A is a 9-membered bicyclic heteroaryl comprising 1 to 5 heteroatoms selected from N, O and S, the remaining ring atoms being carbon; R ¹ is selected from halogen, C _1-6 -alkyl, C _1-6 -alkoxy, halo-C _1-6 -alkyl, hydroxy-C _1-6 -alkyl, C3-6-cycloalkyl-, halo-C1-6-alkyl-C3-6-cycloalkyl-, halo-C1-6-alkoxy, (C1-6-alkyl)2PO-, and a group R ² is selected from hydrogen, halogen, cyano, oxo, C _1-6 -alkyl and halo-C _1-6 -alkyl; R ³ is selected from C _1-6 -alkyl and halo-C _1-6 -alkyl; X is selected from O and NH; or R ⁴ and R ⁵ are each independently selected from hydrogen, halogen and C1-6-alkyl; and B is selected from: In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: (i) A is phenyl; R ¹ is selected from (C 1-6-alkyl)2PO- and a group ; R ² is selected from hydrogen, halogen, cyano, C _1-6 -alkyl and halo-C _1-6 -alkyl; R ³ is selected from C1-6-alkyl and halo-C1-6-alkyl; and X is selected from O and NH; or (ii) A is pyridyl; R ¹ is selected from halogen, C _1-6 -alkyl, C _1-6 -alkoxy, halo-C _1-6 -alkyl, hydroxy-C _1-6 - alkyl, C3-6-cycloalkyl-, halo-C1-6-alkyl-C3-6-cycloalkyl-, halo-C1-6-alkoxy, (C1- 6-alkyl) ₂ PO-, and a group R ² is selected from hydrogen, halogen, cyano, C1-6-alkyl and halo-C1-6-alkyl; R ³ is selected from C1-6-alkyl and halo-C1-6-alkyl; and X is selected from O and NH; or (iii) A is selected from 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,2,4- triazolyl, triazolyl, thiazolyl, imidazolyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, oxazolyl, 1,2-dihydropyridyl, [1,2,4]triazolo[4,3-a]pyridine, [1,2,4]triazolo[1,5-a]pyridine, 1H-pyrrolo[2,3-b]pyridine, imidazo[1,5- a]pyridine, imidazo[1,2-a]pyridine, 2H-pyrazolo[3,4-b]pyridine, 2H- pyrazolo[4,3-b]pyridine, 2H-pyrazolo[4,3-c]pyridine, pyrazolo[1,5- a]pyrimidine, 2H-pyrazolo[3,4-d]pyrimidine, [1,2,4]triazolo[1,5-a]pyrimidine, imidazo[1,2-a]pyrazine, 1,2-benzoxazole, 1H-indazole, and 2H-indazole; R ¹ is selected from halogen, C _1-6 -alkyl, C _1-6 -alkoxy, halo-C _1-6 -alkyl, hydroxy-C _1-6 - alkyl, C _3-6 -cycloalkyl-, halo-C _1-6 -alkyl-C _3-6 -cycloalkyl-, halo-C _1-6 -alkoxy, (C _1- 6-alkyl)2PO-, and a group R ² is selected from hydrogen, halogen, cyano, oxo, C _1-6 -alkyl and halo-C _1-6 -alkyl; R ³ is selected from C _1-6 -alkyl and halo-C _1-6 -alkyl; X is selected from O and NH; R ⁴ and R ⁵ are each independently selected from hydrogen, halogen and C1-6-alkyl; and B is selected from: In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is a compound of formula (Ia) wherein: (i) A is phenyl; R ¹ is selected from (C _1-6 -alkyl) ₂ PO- and a group ; R ² is selected from hydrogen, halogen, cyano, C1-6-alkyl and halo-C1-6-alkyl; R ³ is selected from C1-6-alkyl and halo-C1-6-alkyl; and X is selected from O and NH; or (ii) A is pyridyl; R ¹ is selected from halogen, C _1-6 -alkyl, C _1-6 -alkoxy, halo-C _1-6 -alkyl, halo-C _1-6 - alkyl-C _3-6 -cycloalkyl-, halo-C _1-6 -alkoxy, (C _1-6 -alkyl) ₂ PO-, and a group R ² is selected from hydrogen, halogen, cyano, C _1-6 -alkyl and halo-C _1-6 -alkyl; R ³ is selected from C1-6-alkyl and halo-C1-6-alkyl; and X is selected from O and NH; or (iii) A is selected from 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,2,4- triazolyl, triazolyl, thiazolyl, imidazolyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, oxazolyl, and 1,2-dihydropyridyl; R ¹ is selected from halogen, C _1-6 -alkyl, C _1-6 -alkoxy, halo-C _1-6 -alkyl, halo-C _1-6 - alkyl-C _3-6 -cycloalkyl-, halo-C _1-6 -alkoxy, (C _1-6 -alkyl) ₂ PO-, and a group R ² is selected from hydrogen, halogen, cyano, oxo, C _1-6 -alkyl and halo-C _1-6 -alkyl; R ³ is selected from C1-6-alkyl and halo-C1-6-alkyl; and X is selected from O and NH; and B is selected from: In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: (i) A is phenyl; R ¹ is selected from (C _1-6 -alkyl) ₂ PO- and a group ; R ² is selected from hydrogen, halogen, and halo-C1-6-alkyl; R ³ is selected from C1-6-alkyl, halo-C1-6-alkyl, and (halo-C1-6-alkyl)-(4- to 6- membered heterocyclyl); and X is selected from O and NH; or (ii) A is pyridyl; R ¹ is selected from halogen, C _1-6 -alkyl, C _1-6 -alkoxy, halo-C _1-6 -alkyl, halo-C _1-6 - alkyl-C3-6-cycloalkyl-, halo-C1-6-alkoxy, (C1-6-alkyl)2PO-, and a group R ² is selected from hydrogen, halogen, halo-C _1-6 -alkyl and cyano; R ³ is selected from C1-6-alkyl and halo-C1-6-alkyl; and X is selected from O and NH; or (iii) A is selected from 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,2,4- triazolyl, triazolyl, thiazolyl, imidazolyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, oxazolyl, 1,2-dihydropyridyl, [1,2,4]triazolo[4,3-a]pyridine, [1,2,4]triazolo[1,5-a]pyridine, 1H-pyrrolo[2,3-b]pyridine, imidazo[1,5- a]pyridine, imidazo[1,2-a]pyridine, 2H-pyrazolo[3,4-b]pyridine, 2H- pyrazolo[4,3-b]pyridine, 2H-pyrazolo[4,3-c]pyridine, pyrazolo[1,5- a]pyrimidine, 2H-pyrazolo[3,4-d]pyrimidine, [1,2,4]triazolo[1,5-a]pyrimidine, imidazo[1,2-a]pyrazine, 1,2-benzoxazole, 1H-indazole, 1H-imidazo[1,2- c]pyrimidin-5-one, 1H-pyrrolo[2,3-b]pyridine, imidazo[1,2-a]pyrimidine, 2H- pyrazolo[3,4-c]pyridine, 7H-pyrrolo[2,3-d]pyrimidine, [1,2,4]triazolo[1,5- b]pyrimidine, pyrazolo[1,5-a]pyrimidine, 2H-pyrazolo[4,3-b]pyridine, 1H- imidazo[4,5-b]pyridine, 3H-imidazo[4,5-b]pyridine, 4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine, 1H-pyrazolo[3,4-b]pyridine, 1H- imidazo[1,2-a]pyrimidin-5-one, and 2H-indazole; R ¹ is selected from C1-6-alkoxy, halo-C1-6-alkyl, hydroxy-C1-6-alkyl, C3-6- cycloalkyl-, halo-C1-6-alkyl-C3-6-cycloalkyl-, (halo-C1-6-alkyl)-(3- to 6- membered heterocyclyl)-, halo-C 1-6-alkoxy, and a group ; R ² is selected from hydrogen, halogen, cyano, oxo, C _1-6 -alkyl and halo-C _1-6 -alkyl; R ³ is halo-C1-6-alkyl; and X is selected from O and NH. In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: (i) A is phenyl; R ¹ is selected from (C _1-6 -alkyl) ₂ PO- and a group ; R ² is selected from hydrogen, halogen, and halo-C1-6-alkyl; R ³ is selected from C1-6-alkyl and halo-C1-6-alkyl; and X is selected from O and NH; or (ii) A is pyridyl; R ¹ is selected from halogen, C1-6-alkyl, C1-6-alkoxy, halo-C1-6-alkyl, halo-C1-6- alkyl-C3-6-cycloalkyl-, halo-C1-6-alkoxy, (C1-6-alkyl)2PO-, and a group R ² is selected from hydrogen, halogen, halo-C1-6-alkyl and cyano; R ³ is selected from C1-6-alkyl and halo-C1-6-alkyl; and X is selected from O and NH; or (iii) A is selected from 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,2,4- triazolyl, triazolyl, thiazolyl, imidazolyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, oxazolyl, 1,2-dihydropyridyl, [1,2,4]triazolo[4,3-a]pyridine, [1,2,4]triazolo[1,5-a]pyridine, 1H-pyrrolo[2,3-b]pyridine, imidazo[1,5- a]pyridine, imidazo[1,2-a]pyridine, 2H-pyrazolo[3,4-b]pyridine, 2H- pyrazolo[4,3-b]pyridine, 2H-pyrazolo[4,3-c]pyridine, pyrazolo[1,5- a]pyrimidine, 2H-pyrazolo[3,4-d]pyrimidine, [1,2,4]triazolo[1,5-a]pyrimidine, imidazo[1,2-a]pyrazine, 1,2-benzoxazole, 1H-indazole, and 2H-indazole; R ¹ is selected from C1-6-alkoxy, halo-C1-6-alkyl, hydroxy-C1-6- alkyl, C3-6- cycloalkyl-, halo-C _1-6 -alkyl-C _3-6 -cycloalkyl-, and a group ; R ² is selected from hydrogen, halogen, cyano, oxo, C1-6-alkyl and halo-C1-6-alkyl; R ³ is halo-C1-6-alkyl; and X is selected from O and NH. In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: (i) A is phenyl; R ¹ is selected from (C _1-6 -alkyl) ₂ PO- and a group ; R ² is selected from hydrogen, halogen, and halo-C1-6-alkyl; R ³ is selected from C1-6-alkyl and halo-C1-6-alkyl; and X is selected from O and NH; or (ii) A is pyridyl; R ¹ is selected from halogen, C1-6-alkyl, C1-6-alkoxy, halo-C1-6-alkyl, halo-C1-6- alkyl-C3-6-cycloalkyl-, halo-C1-6-alkoxy, (C1-6-alkyl)2PO-, and a group R ² is selected from hydrogen, halogen, halo-C1-6-alkyl and cyano; R ³ is selected from C1-6-alkyl and halo-C1-6-alkyl; and X is selected from O and NH; or (iii) A is selected from 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,2,4- triazolyl, triazolyl, thiazolyl, imidazolyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, oxazolyl, 1,2-dihydropyridyl, [1,2,4]triazolo[4,3-a]pyridine, [1,2,4]triazolo[1,5-a]pyridine, 1H-pyrrolo[2,3-b]pyridine, imidazo[1,5- a]pyridine, imidazo[1,2-a]pyridine, 2H-pyrazolo[3,4-b]pyridine, 2H- pyrazolo[4,3-b]pyridine, 2H-pyrazolo[4,3-c]pyridine, pyrazolo[1,5- a]pyrimidine, 2H-pyrazolo[3,4-d]pyrimidine, [1,2,4]triazolo[1,5-a]pyrimidine, imidazo[1,2-a]pyrazine, 1,2-benzoxazole, 1H-indazole, and 2H-indazole; R ¹ is selected from C1-6-alkoxy, halo-C1-6-alkyl, hydroxy-C1-6- alkyl, C3-6- cycloalkyl-, halo-C _1-6 -alkyl-C _3-6 -cycloalkyl-, and a group ; R ² is selected from hydrogen, halogen, cyano, oxo, C1-6-alkyl and halo-C1-6-alkyl; R ³ is halo-C1-6-alkyl; and X is selected from O and NH. In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: (i) A is phenyl; R ¹ is selected from (C _1-6 -alkyl) ₂ PO- and a group ; R ² is selected from hydrogen, halogen, and halo-C1-6-alkyl; R ³ is selected from C1-6-alkyl and halo-C1-6-alkyl; and X is selected from O and NH; or (ii) A is pyridyl; R ¹ is selected from halogen, halo-C1-6-alkyl, halo-C1-6-alkoxy, (C1-6-alkyl)2PO-, and a group R ² is selected from hydrogen, halogen, and cyano; R ³ is selected from C1-6-alkyl and halo-C1-6-alkyl; and X is selected from O and NH; or (iii) A is selected from 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,2,4- triazolyl, triazolyl, thiazolyl, imidazolyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, oxazolyl, and 1,2-dihydropyridyl; R ¹ is selected from halo-C1-6-alkyl and halo-C1-6-alkyl-C3-6-cycloalkyl-; and R ² is selected from hydrogen, halogen, cyano, oxo, C1-6-alkyl and halo-C1-6-alkyl. In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: (i) A is phenyl; R ¹ is selected from (C1-6-alkyl)2PO-, a group and a group ; R ² is selected from hydrogen, halogen, and halo-C _1-6 -alkyl; R ^3a is halo-C _1-6 -alkyl; and R ^3b is selected from C1-6-alkyl and halo-C1-6-alkyl; or (ii) A is pyridyl; R ¹ is selected from halogen, halo-C _1-6 -alkyl, halo-C _1-6 -alkoxy, (C _1-6 -alkyl) ₂ PO-, a group and a group ; R ² is selected from hydrogen, halogen, and cyano; R ^3a is halo-C1-6-alkyl; and R ^3b is selected from C _1-6 -alkyl and halo-C _1-6 -alkyl; or (iii) A is selected from 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,2,4- triazolyl, triazolyl, thiazolyl, imidazolyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, oxazolyl, and 1,2-dihydropyridyl; R ¹ is selected from halo-C _1-6 -alkyl and halo-C _1-6 -alkyl-C _3-6 -cycloalkyl-; and R ² is selected from hydrogen, halogen, cyano, oxo, C1-6-alkyl and halo-C1-6-alkyl. In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: (i) A is phenyl; R ¹ is selected from (C _1-6 -alkyl) ₂ PO- and a group ; R ² is selected from hydrogen, halogen, and halo-C _1-6 -alkyl; R ³ is selected from C1-6-alkyl and halo-C1-6-alkyl; and X is O; or (ii) A is pyridyl; R ¹ is selected from halogen and halo-C1-6-alkyl; R ² is selected from hydrogen and halogen; or (iii) A is selected from pyrazinyl and pyrazolyl; R ¹ is halo-C1-6-alkyl; and R ² is hydrogen. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: (i) A is phenyl; R ¹ is selected from (CH ₃ ) ₂ PO- and a group R ² is selected from hydrogen, fluoro, and CF ₃ ; R ³ is selected from methyl and CF3; and X is O; or (ii) A is pyridyl; R ¹ is selected from fluoro and CF3; R ² is selected from hydrogen and fluoro; or (iii) A is selected from pyrazinyl and pyrazolyl; R ¹ is CF ₃ ; and R ² is hydrogen. In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: (i) A is phenyl; R ¹ is selected from (C _1-6 -alkyl) ₂ PO- and a group ; R ² is selected from hydrogen, halogen, and halo-C _1-6 -alkyl; R ³ is selected from C1-6-alkyl and halo-C1-6-alkyl; and X is O; or (ii) A is pyridyl; R ¹ is selected from halogen and halo-C1-6-alkyl; R ² is selected from hydrogen and halogen; or (iii) A is selected from pyrazinyl and pyrazolyl; R ¹ is halo-C1-6-alkyl; and R ² is hydrogen; and B is selected from: In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: (i) A is phenyl; R ² is selected from hydrogen, fluoro, and CF ₃ ; R ³ is selected from methyl and CF3; and X is O; or (ii) A is pyridyl; R ¹ is selected from fluoro and CF ₃ ; R ² is selected from hydrogen and fluoro; or (iii) A is selected from pyrazinyl and pyrazolyl; R ¹ is CF ₃ ; and R ² is hydrogen; and B is selected from: In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: A is phenyl; R ¹ is selected from (C _1-6 -alkyl) ₂ PO- and a group ; R ² is selected from hydrogen, halogen, cyano, C1-6-alkyl and halo-C1-6-alkyl; R ³ is selected from C1-6-alkyl and halo-C1-6-alkyl; and X is selected from O and NH. In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: A is pyridyl; R ¹ is selected from halogen, C1-6-alkyl, C1-6-alkoxy, halo-C1-6-alkyl, halo-C1-6-alkyl-C3- 6-cycloalkyl-, halo-C _1-6 -alkoxy, (C _1-6 -alkyl) ₂ PO-, and a group ; R ² is selected from hydrogen, halogen, cyano, C _1-6 -alkyl and halo-C _1-6 -alkyl; R ³ is selected from C1-6-alkyl and halo-C1-6-alkyl; and X is selected from O and NH. In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: A is pyridyl; R ¹ is selected from halogen, C _1-6 -alkyl, C _1-6 -alkoxy, halo-C _1-6 -alkyl, halo-C _1-6 -alkyl-C _{3- 6} -cycloalkyl-, halo-C _1-6 -alkoxy, (C _1-6 -alkyl) ₂ PO-, and a group ; R ² is selected from hydrogen, halogen, halo-C1-6-alkyl and cyano; R ³ is selected from C _1-6 -alkyl and halo-C _1-6 -alkyl; and X is selected from O and NH. In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: A is selected from 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,2,4- triazolyl, triazolyl, thiazolyl, imidazolyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, oxazolyl, 1,2-dihydropyridyl, [1,2,4]triazolo[4,3-a]pyridine, [1,2,4]triazolo[1,5-a]pyridine, 1H-pyrrolo[2,3-b]pyridine, imidazo[1,5-a]pyridine, imidazo[1,2-a]pyridine, 2H-pyrazolo[3,4-b]pyridine, 2H-pyrazolo[4,3-b]pyridine, 2H-pyrazolo[4,3-c]pyridine, pyrazolo[1,5-a]pyrimidine, 2H-pyrazolo[3,4- d]pyrimidine, [1,2,4]triazolo[1,5-a]pyrimidine, imidazo[1,2-a]pyrazine, 1,2- benzoxazole, 1H-indazole, 1H-imidazo[1,2-c]pyrimidin-5-one, 1H-pyrrolo[2,3- b]pyridine, imidazo[1,2-a]pyrimidine, 2H-pyrazolo[3,4-c]pyridine, 7H-pyrrolo[2,3- d]pyrimidine, [1,2,4]triazolo[1,5-b]pyrimidine, pyrazolo[1,5-a]pyrimidine, 2H- pyrazolo[4,3-b]pyridine, 1H-imidazo[4,5-b]pyridine, 3H-imidazo[4,5-b]pyridine, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine, 1H-pyrazolo[3,4-b]pyridine, 1H- imidazo[1,2-a]pyrimidin-5-one, and 2H-indazole; R ¹ is selected from C _1-6 -alkoxy, halo-C _1-6 -alkyl, hydroxy-C _1-6 -alkyl, C _3-6 -cycloalkyl-, halo-C1-6-alkyl-C3-6-cycloalkyl-, (halo-C1-6-alkyl)-(3- to 6-membered heterocyclyl)-, halo-C1-6-alkoxy, and a group R ² is selected from hydrogen, halogen, cyano, oxo, C1-6-alkyl and halo-C1-6-alkyl; R ³ is halo-C _1-6 -alkyl; and X is selected from O and NH. In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: A is selected from 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,2,4- triazolyl, triazolyl, thiazolyl, imidazolyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, oxazolyl, 1,2-dihydropyridyl, [1,2,4]triazolo[4,3-a]pyridine, [1,2,4]triazolo[1,5-a]pyridine, 1H-pyrrolo[2,3-b]pyridine, imidazo[1,5-a]pyridine, imidazo[1,2-a]pyridine, 2H-pyrazolo[3,4-b]pyridine, 2H-pyrazolo[4,3-b]pyridine, 2H-pyrazolo[4,3-c]pyridine, pyrazolo[1,5-a]pyrimidine, 2H-pyrazolo[3,4- d]pyrimidine, [1,2,4]triazolo[1,5-a]pyrimidine, imidazo[1,2-a]pyrazine, 1,2- benzoxazole, 1H-indazole, and 2H-indazole; R ¹ is selected from C1-6-alkoxy, halo-C1-6-alkyl, hydroxy-C1-6-alkyl, C3-6-cycloalkyl-, halo-C -alkyl-C -cycloalkyl-, 1-6 3-6 and a group ; R ² is selected from hydrogen, halogen, cyano, oxo, C _1-6 -alkyl and halo-C _1-6 -alkyl; R ³ is halo-C _1-6 -alkyl; and X is selected from O and NH. In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: A is selected from 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,2,4- triazolyl, triazolyl, thiazolyl, imidazolyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, oxazolyl, and 1,2-dihydropyridyl; R ¹ is selected from halogen, C1-6-alkyl, C1-6-alkoxy, halo-C1-6-alkyl, halo-C1-6-alkyl-C3- -cycloalkyl-, halo-C -alkox 6 1-6 y, (C1-6-alkyl)2PO-, and a group ; R ² is selected from hydrogen, halogen, cyano, oxo, C _1-6 -alkyl and halo-C _1-6 -alkyl; R ³ is selected from C1-6-alkyl and halo-C1-6-alkyl; and X is selected from O and NH. In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: A is phenyl; R ¹ is selected from (C _1-6 -alkyl) ₂ PO- and a group ; R ² is selected from hydrogen, halogen, and halo-C1-6-alkyl; R ³ is selected from C _1-6 -alkyl and halo-C _1-6 -alkyl; and X is selected from O and NH. In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: A is pyridyl; R ¹ is selected from halogen, halo-C1-6-alkyl, halo-C1-6-alkoxy, (C1-6-alkyl)2PO-, and a group R ² is selected from hydrogen, halogen, and cyano; R ³ is selected from C1-6-alkyl and halo-C1-6-alkyl; and X is selected from O and NH. In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: A is selected from 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,2,4- triazolyl, triazolyl, thiazolyl, imidazolyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, oxazolyl, and 1,2-dihydropyridyl; R ¹ is selected from halo-C1-6-alkyl and halo-C1-6-alkyl-C3-6-cycloalkyl-; and R ² is selected from hydrogen, halogen, cyano, oxo, C _1-6 -alkyl and halo-C _1-6 -alkyl. In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: A is phenyl; R ¹ is selected from (C _1-6 -alkyl) ₂ PO-, a group and a group ; R ² is selected from hydrogen, halogen, and halo-C _1-6 -alkyl; R ^3a is halo-C1-6-alkyl; and R ^3b is selected from C _1-6 -alkyl and halo-C _1-6 -alkyl. In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: A is pyridyl; R ¹ is selected from halogen, halo-C _1-6 -alkyl, halo-C _1-6 -alkoxy, (C _1-6 -alkyl) ₂ PO-, a group R ² is selected from hydrogen, halogen, and cyano; R ^3a is halo-C1-6-alkyl; and R ^3b is selected from C _1-6 -alkyl and halo-C _1-6 -alkyl. In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: A is phenyl; R ¹ is selected from (C _1-6 -alkyl) ₂ PO- and a group ; R ² is selected from hydrogen, halogen, and halo-C1-6-alkyl; R ³ is selected from C _1-6 -alkyl and halo-C _1-6 -alkyl; and X is O. In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: A is pyridyl; R ¹ is selected from halogen and halo-C1-6-alkyl; and R ² is selected from hydrogen and halogen. In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: A is selected from pyrazinyl and pyrazolyl; R ¹ is halo-C _1-6 -alkyl; and R ² is hydrogen. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: A is phenyl; R ¹ is selected from (CH3)2PO- and a group R ² is selected from hydrogen, fluoro, and CF ₃ ; R ³ is selected from methyl and CF ₃ ; and X is O. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: A is pyridyl; R ¹ is selected from fluoro and CF3; and R ² is selected from hydrogen and fluoro. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: A is selected from pyrazinyl and pyrazolyl; R ¹ is CF3; and R ² is hydrogen. In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein A is a 9-membered bicyclic heteroaryl comprising 1 to 5 heteroatoms selected from N, O and S, the remaining ring atoms being carbon. In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein A is a 9-membered bicyclic heteroaryl comprising 1 to 5 nitrogen atoms, the remaining ring atoms being carbon. In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein A is a 9-membered bicyclic heteroaryl comprising 1 to 3 nitrogen atoms, the remaining ring atoms being carbon. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein A is selected from [1,2,4]triazolo[4,3-a]pyridine, [1,2,4]triazolo[1,5-a]pyridine, 1H-pyrrolo[2,3-b]pyridine, imidazo[1,5-a]pyridine, imidazo[1,2-a]pyridine, 2H-pyrazolo[3,4-b]pyridine, 2H-pyrazolo[4,3- b]pyridine, 2H-pyrazolo[4,3-c]pyridine, pyrazolo[1,5-a]pyrimidine, 2H-pyrazolo[3,4- d]pyrimidine, [1,2,4]triazolo[1,5-a]pyrimidine, imidazo[1,2-a]pyrazine, 1,2-benzoxazole, 1H- indazole, and 2H-indazole. In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is selected from: In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is selected from: In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is . In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: R ⁴ is selected from hydrogen, halogen and C _1-6 -alkyl; and R ⁵ is selected from hydrogen and halogen. In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: R ⁴ and R ⁵ are both hydrogen; or R ⁴ and R ⁵ are both halogen; or R ⁴ is C _1-6 -alkyl and R ⁵ is hydrogen. In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: R ⁴ and R ⁵ are both hydrogen; or R ⁴ and R ⁵ are both fluoro; or R ⁴ is methyl and R ⁵ is hydrogen. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R ⁴ and R ⁵ are both hydrogen. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R ⁴ and R ⁵ are both fluoro. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R ⁴ is methyl and R ⁵ is hydrogen. In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: (i) A is phenyl; R ¹ is selected from (C -alk 1-6 yl)2PO- and a group ; R ² is selected from hydrogen, halogen, and halo-C _1-6 -alkyl; R ³ is selected from C _1-6 -alkyl, halo-C _1-6 -alkyl, and (halo-C _1-6 -alkyl)-(4- to 6- membered heterocyclyl); and X is selected from O and NH; or (ii) A is pyridyl; R ¹ is selected from halogen, C _1-6 -alkyl, C _1-6 -alkoxy, halo-C _1-6 -alkyl, halo-C _1-6 - alkyl-C _3-6 -cycloalkyl-, halo-C _1-6 -alkoxy, (C _1-6 -alkyl) ₂ PO-, and a group R ² is selected from hydrogen, halogen, halo-C _1-6 -alkyl and cyano; R ³ is selected from C _1-6 -alkyl and halo-C _1-6 -alkyl; and X is selected from O and NH; or (iii) A is selected from 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,2,4- triazolyl, triazolyl, thiazolyl, imidazolyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, oxazolyl, 1,2-dihydropyridyl, [1,2,4]triazolo[4,3-a]pyridine, [1,2,4]triazolo[1,5-a]pyridine, 1H-pyrrolo[2,3-b]pyridine, imidazo[1,5- a]pyridine, imidazo[1,2-a]pyridine, 2H-pyrazolo[3,4-b]pyridine, 2H- pyrazolo[4,3-b]pyridine, 2H-pyrazolo[4,3-c]pyridine, pyrazolo[1,5- a]pyrimidine, 2H-pyrazolo[3,4-d]pyrimidine, [1,2,4]triazolo[1,5-a]pyrimidine, imidazo[1,2-a]pyrazine, 1,2-benzoxazole, 1H-indazole, 1H-imidazo[1,2- c]pyrimidin-5-one, 1H-pyrrolo[2,3-b]pyridine, imidazo[1,2-a]pyrimidine, 2H- pyrazolo[3,4-c]pyridine, 7H-pyrrolo[2,3-d]pyrimidine, [1,2,4]triazolo[1,5- b]pyrimidine, pyrazolo[1,5-a]pyrimidine, 2H-pyrazolo[4,3-b]pyridine, 1H- imidazo[4,5-b]pyridine, 3H-imidazo[4,5-b]pyridine, 4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine, 1H-pyrazolo[3,4-b]pyridine, 1H- imidazo[1,2-a]pyrimidin-5-one, and 2H-indazole; R ¹ is selected from C _1-6 -alkoxy, halo-C _1-6 -alkyl, hydroxy-C _1-6 -alkyl, C _3-6 - cycloalkyl-, halo-C1-6-alkyl-C3-6-cycloalkyl-, (halo-C1-6-alkyl)-(3- to 6- membered heterocyclyl)-, halo-C 1-6-alkoxy, and a group ; R ² is selected from hydrogen, halogen, cyano, oxo, C1-6-alkyl and halo-C1-6-alkyl; R ³ is halo-C _1-6 -alkyl; X is selected from O and NH; R ⁴ and R ⁵ are both hydrogen; or R ⁴ and R ⁵ are both halogen; or R ⁴ is C1-6-alkyl and R ⁵ is hydrogen; and B is selected from: In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: (i) A is phenyl; R ¹ is selected from (C - 1-6 alkyl)2PO- and a group ; R ² is selected from hydrogen, halogen, and halo-C _1-6 -alkyl; R ³ is selected from C1-6-alkyl and halo-C1-6-alkyl; and X is O; or (ii) A is pyridyl; R ¹ is selected from halogen and halo-C1-6-alkyl; R ² is selected from hydrogen and halogen; or (iii) A is selected from pyrazinyl and pyrazolyl; R ¹ is halo-C _1-6 -alkyl; and R ² is hydrogen; R ⁴ and R ⁵ are both hydrogen; and B is selected from: In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: (i) A is phenyl; R ¹ is selected from (CH3)2PO- and a group R ² is selected from hydrogen, fluoro, and CF ₃ ; R ³ is selected from methyl and CF ₃ ; and X is O; or (ii) A is pyridyl; R ¹ is selected from fluoro and CF3; R ² is selected from hydrogen and fluoro; or (iii) A is selected from pyrazinyl and pyrazolyl; R ¹ is CF3; and R ² is hydrogen; R ⁴ and R ⁵ are both hydrogen; and B is selected from: In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is selected from the group consisting of: (4aR,8aS)-6-[6-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-2-a zaspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[5-(trifluoromethylsulfonyl)-2-pyridyl]methy l]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[3-methyl-5-(trifluoromethyl)pyrazol-1-yl]me thyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin -6-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyrid in-6-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyrid in-5-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[6-[1-(trifluoromethyl)cyclopropyl]-3-pyridy l]methyl]-2-azaspiro[3.3]heptane- 2-carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin- 3-one; (4aR,8aS)-6-[6-[(3,5-difluoro-2-pyridyl)methyl]-2-azaspiro[3 .3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-aza spiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[(5-fluoro-3-pyridyl)methyl]-2-azaspiro[3.3]h eptane-2-carbonyl]-4,4a,5,7,8,8a- hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[(4-fluoro-2-methylsulfonyl-phenyl)methyl]-2- azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[(3-methylsulfonylphenyl)methyl]-2-azaspiro[3 .3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl] -2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[(2-fluoro-4-methylsulfonyl-phenyl)methyl]-2- azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[3-dimethylphosphoryl-5-(trifluoromethyl)phe nyl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; 5-[[2-[(4aR,8aS)-3-oxo-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][ 1,4]oxazine-6-carbonyl]-2- azaspiro[3.3]heptan-6-yl]methyl]-3-(trifluoromethyl)pyridine -2-carbonitrile; 5-[[2-[(4aR,8aS)-3-oxo-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][ 1,4]oxazine-6-carbonyl]-2- azaspiro[3.3]heptan-6-yl]methyl]-2-(trifluoromethyl)pyridine -3-carbonitrile; (4aR,8aS)-6-[6-[[5-(trifluoromethylsulfonyl)-2-pyridyl]methy l]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- on; (4aR,8aS)-6-[6-[[5-(trifluoromethylsulfonyl)-3-pyridyl]methy l]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; rac-(4aR,8aS)-6-[6-[[5-(trifluoromethylsulfonimidoyl)-2-pyri dyl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[5-[1-(trifluoromethyl)cyclopropyl]-1,3,4-ox adiazol-2-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-tr iazol-1-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[5-[1-(trifluoromethyl)cyclopropyl]-1H-1,2,4 -triazol-3-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[4-[1-(trifluoromethyl)cyclopropyl]pyrazol-1 -yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[4-[1-(trifluoromethyl)cyclopropyl]imidazol- 1-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-fluoro-5-(trifluoromethyl)-2-pyridyl]meth yl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[6-(trifluoromethoxy)-3-pyridyl]methyl]-2-az aspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[5-(trifluoromethoxy)-2-pyridyl]methyl]-2-az aspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[2-oxo-4-(trifluoromethyl)-1-pyridyl]methyl] -2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[2-oxo-5-(trifluoromethyl)-1-pyridyl]methyl] -2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[(5-methylsulfonyl-3-pyridyl)methyl]-2-azaspi ro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[(5-methylsulfonyl-2-pyridyl)methyl]-2-azaspi ro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[(5-dimethylphosphoryl-2-pyridyl)methyl]-2-az aspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-1,2,4-thiadiazol-5-yl]m ethyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[2-methyl-5-(trifluoromethyl)triazol-4-yl]me thyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]me thyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]me thyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]me thyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[4-(2,2,2-trifluoroethyl)pyrazol-1-yl]methyl ]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[1-methyl-4-(trifluoromethyl)pyrazol-3-yl]me thyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[3-methyl-5-(trifluoromethyl)pyrazol-1-yl]me thyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]me thyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]methyl ]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[6-(trifluoromethyl)pyridazin-3-yl]methyl]-2 -azaspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[5-(trifluoromethyl)pyrimidin-2-yl]methyl]-2 -azaspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[2-(trifluoromethyl)pyrimidin-5-yl]methyl]-2 -azaspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[6-(trifluoromethyl)pyrimidin-4-yl]methyl]-2 -azaspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[2-(trifluoromethyl)pyrimidin-4-yl]methyl]-2 -azaspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[4-(trifluoromethyl)pyrimidin-2-yl]methyl]-2 -azaspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2-aza spiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[4-(trifluoromethyl)-2-pyridyl]methyl]-2-aza spiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[5-(trifluoromethyl)-3-pyridyl]methyl]-2-aza spiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]me thyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]me thyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-1,2,4-triazol-1-yl]meth yl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[4-(trifluoromethyl)triazol-2-yl]methyl]-2-a zaspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[5-(trifluoromethyl)-1,2,4-triazol-1-yl]meth yl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]m ethyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[4-(trifluoromethyl)oxazol-2-yl]methyl]-2-az aspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[4-(trifluoromethyl)pyrazol-1-yl]methyl]-2-a zaspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[4-(trifluoromethyl)imidazol-1-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[2-(trifluoromethyl)imidazol-1-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]-2-a zaspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-(difluoromethyl)-5-methyl-pyrazol-1-yl]me thyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[5-(difluoromethyl)-3-methyl-pyrazol-1-yl]me thyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[(5-chloro-3-fluoro-2-pyridyl)methyl]-2-azasp iro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[(3-chloro-5-fluoro-2-pyridyl)methyl]-2-azasp iro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-(difluoromethyl)-1H-pyrazol-5-yl]methyl]- 2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[(5-chloro-3-pyridyl)methyl]-2-azaspiro[3.3]h eptane-2-carbonyl]-4,4a,5,7,8,8a- hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[(5-chloro-2-pyridyl)methyl]-2-azaspiro[3.3]h eptane-2-carbonyl]-4,4a,5,7,8,8a- hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[(5-fluoro-2-pyridyl)methyl]-2-azaspiro[3.3]h eptane-2-carbonyl]-4,4a,5,7,8,8a- hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-fluoro-5-(trifluoromethylsulfonyl)phenyl] methyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; rac-(4aR,8aS)-6-[6-[[3-fluoro-5-(trifluoromethylsulfonimidoy l)phenyl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; rac-(4aR,8aS)-6-[6-[[2-fluoro-4-(trifluoromethylsulfonimidoy l)phenyl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; rac-(4aR,8aS)-6-[6-[[2-(methylsulfonimidoyl)-4-(trifluoromet hyl)phenyl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; rac-(4aR,8aS)-6-[6-[[4-(methylsulfonimidoyl)-3-(trifluoromet hyl)phenyl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; rac-(4aR,8aS)-6-[6-[[3-(methylsulfonimidoyl)-5-(trifluoromet hyl)phenyl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[3-dimethylphosphoryl-5-(trifluoromethyl)benz yl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[3-(trifluoromethylsulfonyl)phenyl]methyl]-2 -azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2 -azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[4-([S(R)]-trifluoromethylsulfonimidoyl)phen yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[4-([S(S)]-trifluoromethylsulfonimidoyl)phen yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[4-([S(S)]-trifluoromethylsulfonimidoyl)phen yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one ; (4aR,8aS)-6-[6-[[4-([S(R)]-trifluoromethylsulfonimidoyl)phen yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-([S(R)]-trifluoromethylsulfonimidoyl)phen yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one ; (4aR,8aS)-6-[6-[[3-([S(S)]-trifluoromethylsulfonimidoyl)phen yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-([S(S)]-trifluoromethylsulfonimidoyl)phen yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one ; (4aR,8aS)-6-[6-[[3-([S(R)]-trifluoromethylsulfonimidoyl)phen yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; rac-(4aR,8aS)-6-[6-[[4-fluoro-2-(methylsulfonimidoyl)phenyl] methyl]-2-azaspiro[3.3]heptane- 2-carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin- 3-one; (4aR,8aS)-6-[6-[(3-dimethylphosphoryl-5-fluoro-phenyl)methyl ]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; rac-(4aR,8aS)-6-[6-[[4-(methylsulfonimidoyl)phenyl]methyl]-2 -azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; rac-(4aR,8aS)-6-[6-[[3-(methylsulfonimidoyl)phenyl]methyl]-2 -azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[(3-dimethylphosphorylphenyl)methyl]-2-azaspi ro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[7-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-2-a zaspiro[3.5]nonane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[7-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2-aza spiro[3.5]nonane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[7-[(3,5-difluoro-2-pyridyl)methyl]-2-azaspiro[3 .5]nonane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[7-[(5-fluoro-2-pyridyl)methyl]-2-azaspiro[3.5]n onane-2-carbonyl]-4,4a,5,7,8,8a- hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[7-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-aza spiro[3.5]nonane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[7-[[6-(difluoromethoxy)-3-pyridyl]methyl]-2-aza spiro[3.5]nonane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; 5-[[(6S)-2-[(4aR,8aS)-3-oxo-4,4a,5,7,8,8a-hexahydropyrido[4, 3-b][1,4]oxazine-6-carbonyl]-2- azaspiro[3.4]octan-6-yl]methyl]-2-(trifluoromethyl)pyridine- 4-carbonitrile; 5-[[(6R)-2-[(4aR,8aS)-3-oxo-4,4a,5,7,8,8a-hexahydropyrido[4, 3-b][1,4]oxazine-6-carbonyl]-2- azaspiro[3.4]octan-6-yl]methyl]-2-(trifluoromethyl)pyridine- 4-carbonitrile; (4aR,8aS)-6-[(6S)-6-[[5-(trifluoromethyl)pyrazin-2-yl]methyl ]-2-azaspiro[3.4]octane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[(6R)-6-[[5-(trifluoromethyl)pyrazin-2-yl]methyl ]-2-azaspiro[3.4]octane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-aza spiro[3.4]octane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[(6R)-6-[[4-(trifluoromethylsulfonyl)phenyl]meth yl]-2-azaspiro[3.4]octane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[(6R)-6-[[3-(trifluoromethylsulfonyl)phenyl]meth yl]-2-azaspiro[3.4]octane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aS,8aR)-6-[6-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-2-a zaspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aS,8aR)-6-[6-[[5-(trifluoromethyl)pyrimidin-2-yl]methyl]-2 -azaspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aS,8aR)-6-[6-[[6-(trifluoromethoxy)-3-pyridyl]methyl]-2-az aspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aS,8aR)-6-[6-[[2-oxo-4-(trifluoromethyl)-1-pyridyl]methyl] -2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aS,8aR)-6-[6-[[5-(trifluoromethylsulfonyl)-2-pyridyl]methy l]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aS,8aR)-6-[6-[[4-(trifluoromethyl)oxazol-2-yl]methyl]-2-az aspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aS,8aR)-6-[6-[[4-(trifluoromethyl)imidazol-1-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aS,8aR)-6-[6-[[3-(trifluoromethyl)-1,2,4-triazol-1-yl]meth yl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aS,8aR)-6-[6-[(3-chloro-5-fluoro-2-pyridyl)methyl]-2-azasp iro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aS,8aR)-6-[6-[(5-chloro-3-pyridyl)methyl]-2-azaspiro[3.3]h eptane-2-carbonyl]-4,4a,5,7,8,8a- hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aS,8aR)-6-[7-[(5-fluoro-2-pyridyl)methyl]-2-azaspiro[3.5]n onane-2-carbonyl]-4,4a,5,7,8,8a- hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aS,8aR)-6-[7-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2-aza spiro[3.5]nonane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[2-(trifluoromethyl)imidazo[1,2-a]pyrazin-6- yl]methyl]-2-azaspiro[3.3]heptane- 2-carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin- 3-one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-1H-pyrazolo[4,3-b]pyrid in-5-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]p yridin-6-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]p yridin-6-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin -6-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-1H-indazol-6-yl]methyl] -2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrim idin-6-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-1H-pyrazolo[4,3-c]pyrid in-6-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyrid in-5-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-1H-indazol-5-yl]methyl] -2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)imidazo[1,5-a]pyridin-6- yl]methyl]-2-azaspiro[3.3]heptane- 2-carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin- 3-one; (4aR,8aS)-6-[6-[[1-(trifluoromethyl)indazol-6-yl]methyl]-2-a zaspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)indoxazen-5-yl]methyl]-2 -azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[2-(trifluoromethyl)imidazo[1,2-a]pyridin-6- yl]methyl]-2-azaspiro[3.3]heptane- 2-carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin- 3-one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridi n-6-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[5-[1-(trifluoromethyl)cyclopropyl]pyrimidin -2-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[2-[1-(trifluoromethyl)cyclopropyl]pyrimidin -5-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-methoxy-5-(trifluoromethyl)pyrazin-2-yl]m ethyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[5-[1-(trifluoromethyl)cyclopropyl]-2-pyridy l]methyl]-2-azaspiro[3.3]heptane- 2-carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin- 3-one; (4aR,8aS)-6-[6-[[1-methyl-3-(trifluoromethyl)pyrrolo[2,3-b]p yridin-6-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[5-(trifluoromethyl)-1H-pyrazol-4-yl]methyl] -2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[(4-triflylpyrazol-1-yl)methyl]-2-azaspiro[3. 3]heptane-2-carbonyl]-4,4a,5,7,8,8a- hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]p yridin-7-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[6-[1-(trifluoromethyl)cyclopropyl]-3-pyridy l]methyl]-2-azaspiro[3.3]heptane- 2-carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin- 3-one; (4aR,8aS)-6-[6-[[5-[1-(trifluoromethyl)cyclopropyl]-1H-pyraz ol-3-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[1-cyclopropyl-3-(trifluoromethyl)pyrazol-4- yl]methyl]-2-azaspiro[3.3]heptane- 2-carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin- 3-one; (4aR,8aS)-6-[6-[[5-[1-(trifluoromethyl)cyclopropyl]pyrazin-2 -yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[6-[1-(trifluoromethyl)cyclopropyl]pyridazin -3-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; rac-(4aR,8aS)-6-[6-[[4-(trifluoromethylsulfonimidoyl)pyrazol -1-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]p yrimidin-6-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[2-(2,2,2-trifluoroethyl)triazol-4-yl]methyl ]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]p yridin-6-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[2-methyl-4-(trifluoromethyl)pyrazol-3-yl]me thyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[4-(trifluoromethyl)thiazol-2-yl]methyl]-2-a zaspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[2-(2,2,2-trifluoroethyl)-5-(trifluoromethyl )pyrazol-3-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[1-(trifluoromethyl)pyrazol-4-yl]methyl]-2-a zaspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[3-mesyl-5-(trifluoromethyl)benzyl]-2-azaspir o[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[4-(trifluoromethyl)triazol-1-yl]methyl]-2-a zaspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[1-(2,2,2-trifluoroethyl)-3-(trifluoromethyl )pyrazol-4-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[1-(2-hydroxyethyl)-3-(trifluoromethyl)pyrro lo[2,3-b]pyridin-6-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aS,8aR)-6-[6-[[5-[1-(trifluoromethyl)cyclopropyl]-1,3,4-ox adiazol-2-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[difluoro-[2-methoxy-6-(trifluoromethyl)-3-py ridyl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[(1R)-1-[4-methyl-5-(trifluoromethyl)-2-pyrid yl]ethyl]-2-azaspiro[3.3]heptane- 2-carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin- 3-one; (4aR,8aS)-6-[6-[(1S)-1-[4-methyl-5-(trifluoromethyl)-2-pyrid yl]ethyl]-2-azaspiro[3.3]heptane- 2-carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin- 3-one; (4aR,8aS)-6-[6-[difluoro-[2-(trifluoromethyl)-4-pyridyl]meth yl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[difluoro-[2-(trifluoromethyl)pyrimidin-5-yl] methyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[difluoro-[6-(trifluoromethyl)-3-pyridyl]meth yl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]p yridin-7-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-1H-pyrazolo[3,4-c]pyrid in-5-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[5-(trifluoromethyl)-7H-pyrrolo[2,3-d]pyrimi din-2-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridi n-5-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[2-(trifluoromethyl)imidazo[1,2-a]pyridin-7- yl]methyl]-2-azaspiro[3.3]heptane- 2-carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin- 3-one; (4aR,8aS)-6-[6-[4-[3-(trifluoromethyl)azetidin-1-yl]sulfonyl benzyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[6-[1-(trifluoromethyl)cyclopropyl]-2-pyridy l]methyl]-2-azaspiro[3.3]heptane- 2-carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin- 3-one; (4aR,8aS)-6-[6-[[2-[1-(trifluoromethyl)cyclopropyl]pyrimidin -4-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[4-[1-(trifluoromethyl)cyclopropyl]-2-pyridy l]methyl]-2-azaspiro[3.3]heptane- 2-carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin- 3-one; (4aR,8aS)-6-[6-[[5-[1-(trifluoromethyl)cyclopropyl]-3-pyridy l]methyl]-2-azaspiro[3.3]heptane- 2-carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin- 3-one; (4aR,8aS)-6-[6-[[2-[1-(trifluoromethyl)cyclopropyl]-4-pyridy l]methyl]-2-azaspiro[3.3]heptane- 2-carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin- 3-one; (4aR,8aS)-6-[6-[difluoro-[6-(trifluoromethoxy)-3-pyridyl]met hyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[1-(2,2,2-trifluoroethyl)-5-(trifluoromethyl )pyrazol-3-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[3-mesyl-4-(trifluoromethyl)benzyl]-2-azaspir o[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)imidazo[1,2-a]pyrimidin- 7-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[difluoro-[2-methoxy-5-(trifluoromethyl)-3-py ridyl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[5-[3-(trifluoromethyl)azetidin-1-yl]pyrazin -2-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)indoxazen-6-yl]methyl]-2 -azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[2-keto-4-[1-(trifluoromethyl)cyclopropyl]-1 -pyridyl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-ox adiazol-5-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-ox adiazol-3-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[(5-keto-1H-imidazo[1,2-c]pyrimidin-7-yl)meth yl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[5-[1-(trifluoromethyl)cyclopropyl]imidazol- 1-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[difluoro-[6-(trifluoromethyl)pyridazin-3-yl] methyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[difluoro-[5-(trifluoromethyl)pyrimidin-2-yl] methyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[1-(2,2,2-trifluoroethyl)-1,2,4-triazol-3-yl ]methyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[4-(trifluoromethyl)-1H-pyrazol-3-yl]methyl] -2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[6-[1-(trifluoromethyl)cyclopropyl]pyrimidin -4-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[difluoro-[5-(trifluoromethyl)pyrazin-2-yl]me thyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[2-oxo-5-[1-(trifluoromethyl)cyclopropyl]-1- pyridyl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[5-oxo-1-(2,2,2-trifluoroethyl)imidazo[1,2-a ]pyrimidin-7-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[2-(trifluoromethyl)-[1,2,4]triazolo[1,5-b]p yridazin-6-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[2-(trifluoromethyl)imidazo[1,2-a]pyrimidin- 6-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[6-[1-(trifluoromethyl)cyclopropyl]pyrazin-2 -yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[7-[[2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin -6-yl]methyl]-2- azaspiro[3.5]nonane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyrid o[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[7-[[2-(trifluoromethyl)imidazo[1,2-a]pyrazin-6- yl]methyl]-2-azaspiro[3.5]nonane- 2-carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin- 3-one; (4aR,8aS)-6-[7-[[3-(trifluoromethyl)-1H-pyrazolo[4,3-c]pyrid in-6-yl]methyl]-2- azaspiro[3.5]nonane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyrid o[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[7-[[3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrim idin-6-yl]methyl]-2- azaspiro[3.5]nonane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyrid o[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[2-[[3-(trifluoromethyl)-1H-pyrazolo[4,3-b]pyrid in-5-yl]methyl]-7- azaspiro[3.5]nonane-7-carbonyl]-4,4a,5,7,8,8a-hexahydropyrid o[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[2-[[3-(trifluoromethyl)-1H-pyrazolo[4,3-c]pyrid in-6-yl]methyl]-7- azaspiro[3.5]nonane-7-carbonyl]-4,4a,5,7,8,8a-hexahydropyrid o[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[2-[[3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrim idin-6-yl]methyl]-7- azaspiro[3.5]nonane-7-carbonyl]-4,4a,5,7,8,8a-hexahydropyrid o[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[2-[[2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin -6-yl]methyl]-7- azaspiro[3.5]nonane-7-carbonyl]-4,4a,5,7,8,8a-hexahydropyrid o[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[5-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyrid in-3-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[2-(trifluoromethyl)-3H-imidazo[4,5-b]pyridi n-6-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[2-(trifluoromethyl)-1H-imidazo[4,5-b]pyridi n-5-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-(1H-pyrazolo[4,3-b]pyridin-5-ylmethyl)-2-azas piro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[(5-methoxypyrrolo[2,3-c]pyridin-1-yl)methyl] -2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[1-methyl-3-(trifluoromethyl)pyrazolo[3,4-b] pyridin-6-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; rac-(4aR,8aS)-6-[7-[[2-(trifluoromethyl)-4,5,6,7-tetrahydrop yrazolo[1,5-a]pyrimidin-6- yl]methyl]-2-azaspiro[3.5]nonane-2-carbonyl]-4,4a,5,7,8,8a-h exahydropyrido[4,3- b][1,4]oxazin-3-one; and (4aR,8aS)-6-[6-[[4-[1-(trifluoromethyl)cyclopropyl]pyrimidin -2-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one. In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is selected from the group consisting of: (4aR,8aS)-6-[6-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-2-a zaspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[(3,5-difluoro-2-pyridyl)methyl]-2-azaspiro[3 .3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-aza spiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl] -2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[(2-fluoro-4-methylsulfonyl-phenyl)methyl]-2- azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[3-dimethylphosphoryl-5-(trifluoromethyl)phe nyl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one; (4aR,8aS)-6-[(6R)-6-[[4-(trifluoromethylsulfonyl)phenyl]meth yl]-2-azaspiro[3.4]octane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyrid in-6-yl]methyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyrid in-5-yl]methyl]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one; and (4aR,8aS)-6-[(6R)-6-[[3-(trifluoromethylsulfonyl)phenyl]meth yl]-2-azaspiro[3.4]octane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is (4aR,8aS)-6-[6-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-2-a zaspiro[3.3]heptane- 2-carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin- 3-one. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is (4aR,8aS)-6-[6-[(3,5-difluoro-2-pyridyl)methyl]-2-azaspiro[3 .3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is (4aR,8aS)-6-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-aza spiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl] -2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is (4aR,8aS)-6-[6-[(2-fluoro-4-methylsulfonyl-phenyl)methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is (4aR,8aS)-6-[6-[[3-dimethylphosphoryl-5-(trifluoromethyl)phe nyl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is (4aR,8aS)-6-[(6R)-6-[[4-(trifluoromethylsulfonyl)phenyl]meth yl]-2- azaspiro[3.4]octane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyrid o[4,3-b][1,4]oxazin-3-one. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyrid in-6-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyrid in-5-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is (4aR,8aS)-6-[(6R)-6-[[3-(trifluoromethylsulfonyl)phenyl]meth yl]-2- azaspiro[3.4]octane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyrid o[4,3-b][1,4]oxazin-3-one. In a particular embodiment, the present invention provides pharmaceutically acceptable salts of the compounds according to formula (I) as described herein, especially hydrochloride salts. In a further particular embodiment, the present invention provides compounds according to formula (I) as described herein. In some embodiments, the compounds of formula (I) are isotopically-labeled by having one or more atoms therein replaced by an atom having a different atomic mass or mass number. Such isotopically-labeled (i.e., radiolabeled) compounds of formula (I) are considered to be within the scope of this disclosure. Examples of isotopes that can be incorporated into the compounds of formula (I) include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, sulfur, fluorine, chlorine, and iodine, such as, but not limited to, ² H, ³ H, ¹¹ C, ¹³ C, ¹⁴ C, ¹³ N, ¹⁵ N, ¹⁵ O, ¹⁷ O, ¹⁸ O, ³¹ P, ³² P, ³⁵ S, ¹⁸ F, ³⁶ Cl, ¹²³ I, and ¹²⁵ I, respectively. Certain isotopically-labeled compounds of formula (I), for example, those incorporating a radioactive isotope, are useful in drug and/or substrate tissue distribution studies. The radioactive isotopes tritium, i.e. ³ H, and carbon-14, i.e., ¹⁴ C, are particularly useful for this purpose in view of their ease of incorporation and ready means of detection. For example, a compound of formula (I) can be enriched with 1, 2, 5, 10, 25, 50, 75, 90, 95, or 99 percent of a given isotope. Substitution with heavier isotopes such as deuterium, i.e. ² H, may afford certain therapeutic advantages resulting from greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements. Substitution with positron emitting isotopes, such as ¹¹ C, ¹⁸ F, ¹⁵ O and ¹³ N, can be useful in Positron Emission Topography (PET) studies for examining substrate receptor occupancy. Isotopically-labeled compounds of formula (I) can generally be prepared by conventional techniques known to those skilled in the art or by processes analogous to those described in the Examples as set out below using an appropriate isotopically-labeled reagent in place of the non- labeled reagent previously employed. Processes of Manufacturing The preparation of compounds of formula (I) of the present invention may be carried out in sequential or convergent synthetic routes. Syntheses of the invention are shown in the following general schemes. The skills required for carrying out the reaction and purification of the resulting products are known to those persons skilled in the art. The substituents and indices used in the following description of the processes have the significance given herein, unless indicated to the contrary. If one of the starting materials, intermediates or compounds of formula (I) contain one or more functional groups which are not stable or are reactive under the reaction conditions of one or more reaction steps, appropriate protective groups (as described e.g., in “Protective Groups in Organic Chemistry” by T. W. Greene and P. G. M. Wutts, 5th Ed., 2014, John Wiley & Sons, N.Y.) can be introduced before the critical step applying methods well known in the art. Such protective groups can be removed at a later stage of the synthesis using standard methods described in the literature. If starting materials or intermediates contain stereogenic centers, compounds of formula (I) can be obtained as mixtures of diastereomers or enantiomers, which can be separated by methods well known in the art e.g., chiral HPLC, chiral SFC or chiral crystallization. Racemic compounds can e.g., be separated into their antipodes via diastereomeric salts by crystallization with optically pure acids or by separation of the antipodes by specific chromatographic methods using either a chiral adsorbent or a chiral eluent. It is equally possible to separate starting materials and intermediates containing stereogenic centers to afford diastereomerically/enantiomerically enriched starting materials and intermediates. Using such diastereomerically/enantiomerically enriched starting materials and intermediates in the synthesis of compounds of formula (I) will typically lead to the respective diastereomerically/enantiomerically enriched compounds of formula (I). A person skilled in the art will acknowledge that in the synthesis of compounds of formula (I) - insofar not desired otherwise - an “orthogonal protection group strategy” will be applied, allowing the cleavage of several protective groups one at a time each without affecting other protective groups in the molecule. The principle of orthogonal protection is well known in the art and has also been described in literature (e.g. Barany and R. B. Merrifield, J. Am. Chem. Soc. 1977, 99, 7363; H. Waldmann et al., Angew. Chem. Int. Ed. Engl.1996, 35, 2056). A person skilled in the art will acknowledge that the sequence of reactions may be varied depending on reactivity and nature of the intermediates. In more detail, the compounds of formula (I) can be manufactured by the methods given below, by the methods given in the examples or by analogous methods. Appropriate reaction conditions for the individual reaction steps are known to a person skilled in the art. Also, for reaction conditions described in literature affecting the described reactions see for example: Comprehensive Organic Transformations: A Guide to Functional Group Preparations, 2nd Edition, Richard C. Larock. John Wiley & Sons, New York, NY.1999). It was found convenient to carry out the reactions in the presence or absence of a solvent. There is no particular restriction on the nature of the solvent to be employed, provided that it has no adverse effect on the reaction or the reagents involved and that it can dissolve the reagents, at least to some extent. The described reactions can take place over a wide range of temperatures, and the precise reaction temperature is not critical to the invention. It is convenient to carry out the described reactions in a temperature range between -78 °C to reflux. The time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents. However, a period of from 0.5 hours to several days will usually suffice to yield the described intermediates and compounds. The reaction sequence is not limited to the one displayed in the schemes, however, depending on the starting materials and their respective reactivity, the sequence of reaction steps can be freely altered. If starting materials or intermediates are not commercially available or their synthesis not described in literature, they can be prepared in analogy to existing procedures for close analogues or as outlined in the experimental section. The following abbreviations are used in the present text: AcOH = acetic acid, ACN = acetonitrile , Bn = benzyl, BINAP = (2,2'-bis(diphenylphosphino)- 1,1'-binaphthyl), Boc = tert-butyloxycarbonyl, CAS RN = chemical abstracts registration number, Cbz = benzyloxycarbonyl, Cs ₂ CO ₃ = cesium carbonate, CO = carbon monoxide, CuCl = copper(I) chloride, CuCN = copper(I) cyanide, CuI = copper(I) iodide, DABCO = 1,4- Diazabicyclo[2.2.2]octane;triethylenediamine, DAST = (diethylamino)sulfur trifluoride, DBU = 1,8-diazabicyclo[5,4,0]undec-7-ene, DCE = 1,2-dichloroethane, DEAD = diethyl azodicarboxylate, DIAD = diisopropyl azodicarboxylate, DIBAL-H = diisobutyl aluminium hydride, DMAP = 4-dimethylaminopyridine, DME = dimethoxyethane , DMEDA = N,N’- dimethylethylenediamine, DMF = N,N-dimethylformamide, DIPEA = N,N- diisopropylethylamine, dppf = 1,1 bis(diphenyl phosphino)ferrocene, EDC.HCl = N-(3- dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride, EI = electron impact, ESI = electrospray ionization, EtOAc = ethyl acetate, EtOH = ethanol, h = hour(s), FA = formic acid, H2O = water, H2SO4 = sulfuric acid, HATU = 1-[bis(dimethylamino)methylene]-1H-1,2,3- triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate, HBTU = O-benzotriazole-N,N,N’,N’- tetramethyl-uronium-hexafluoro-phosphate, HCl = hydrogen chloride, HOBt = 1-hydroxy-1H- benzotriazole; HPLC = high performance liquid chromatography, iPrMgCl = isopropylmagnesium chloride, I2 = iodine, IPA = 2-propanol, ISP = ion spray positive (mode), ISN = ion spray negative (mode), K2CO3 = potassium carbonate, KHCO3 = potassium bicarbonate, KI = potassium iodide, KOH = potassium hydroxide, K3PO4 = potassium phosphate tribasic, LiAlH ₄ or LAH = lithium aluminium hydride, LiHMDS = lithium bis(trimethylsilyl)amide, LiOH = lithium hydroxide, mCPBA = meta-chloroperoxybenzoic acid, MgSO4 = magnesium sulfate, min = minute(s), mL = milliliter, MPLC = medium pressure liquid chromatography, MS = mass spectrum, MTBE = tert-butylmethylether, nBuLi = n-butyllithium, NaBH ₃ CN = sodium cyanoborohydride, NaH = sodium hydride, NBS = N-bromosuccinimide, NaHCO3 = sodium hydrogen carbonate, NaNO2 = sodium nitrite, NaBH(OAc)3 = sodium triacetoxyborohydride, NaOH = sodium hydroxide, Na2CO3 = sodium carbonate, Na2SO4 = sodium sulfate, Na ₂ S ₂ O ₃ = sodium thiosulfate, NEt ₃ = triethylamine (TEA), NH ₄ Cl = ammonium chloride, NMP = N-methyl-2-pyrrolidone, OAc = Acetoxy, T3P = propylphosphonic anhydride, PE = petroleum ether, PG = protective group, Pd-C = palladium on activated carbon, PdCl2(dppf)-CH ₂ Cl ₂ = 1,1'-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex, Pd ₂ (dba) ₃ = tris(dibenzylideneacetone)dipalladium(0), Pd(OAc) ₂ = palladium(II) acetate, Pd(OH)2 = palladium hydroxide, Pd(PPh3)4 = tetrakis(triphenylphosphine)palladium(0), PMP = 1,2,2,6,6-Pentamethylpiperidine, PTSA = p- toluenesulfonic acid, R = any group, RP = reverse phase, RT = room temperature, SFC = Supercritical Fluid Chromatography, S-PHOS = 2-dicyclohexylphosphino-2',6'- dimethoxybiphenyl, TBAI = tetra butyl ammonium iodine, TEA = triethylamine, TFA = trifluoroacetic acid, THF = tetrahydrofuran, TMEDA = N,N,N',N'-tetramethylethylenediamine, TS-TPP = triphenylphospine – polymer bound, ZnCl2 = zinc chloride, Hal = halogen, prep-TLC = preparative thin layer chromatography. The present compounds of formula I can be prepared by reacting an activated intermediate of formula 2 with the nucleophilic spirocyclic amine 1 by heating in a solvent such as DMF or CH3CN in the presence of a base such as DIPEA. (Scheme 1). Alternatively the activated intermediate can be formed on the other coupling partner (1) that will make the urea of formula I. I 1 ₂ Scheme 1 The activated intermediate 2 can be generated transiently in the reaction mixture, or by reacting an amine 3 with a coupling agent such as di(1H-1,2,4-triazol-1-yl)methanone (4) in a solvent such as acetonitrile in the presence of a base such as DIPEA (Scheme 2). Alternatively, the same strategy as in Schemes 1 and 2 may be used, but with the activated intermediate being constructed initially on spirocyclic amine 1, before coupling with amine 3. Scheme 2 Building blocks of formula 1 can be generated by Suzuki reaction (e.g. (Pd(dppf)Cl ₂ , K ₂ CO ₃ , dioxane/H2O), (X = Br, I) followed by hydrogenation (e.g. Pd/C, H2) and deprotection (e.g. using TsOH or TFA when PG =Boc) (Scheme 3). The required boronate intermediate 5 can be generated by reacting a ketone with 4,4,5,5-tetramethyl-2-[(tetramethyl-1,3,2-dioxaborolan-2- yl)methyl]-1,3,2-dioxaborolane (LiTMP, THF, -78 ºC). Where A = N-linked heteroaryl, a Chan- Lam type coupling can be used in place of the Suzuki reaction (e.g. using Cu(OAc)2 under oxygen atmosphere), followed by the hydrogenation/deprotection. A similar sequence could also be used to generate building blocks where e.g. R ₄ = Me and R ₅ = H starting from a suitably functionalized boronate 5, with an additional Me group on the alkene carbon bearing the boronate. In some cases, where A = heteroaryl with a free N-H group (e.g. N-H pyrazole or a fused N-H pyrazole) it was beneficial to use an additional protecting group on the N-H group (e.g. SEM protection, which could be introduced using standard techniques, and typically could be deprotected in the final deprotection step under acidic conditions). 6 ₅ 7 1 Scheme 3 Alternatively, building blocks of formula 1, where A = N linked heteroaryl, can be prepared by reacting nucleophilic heterocycle A (8), with a suitably protected building block 9 (X = leaving group such as OMs, I, Br) in the presence of a base such as Cs2CO3, followed by deprotection under standard conditions (e.g. with TsOH when PG = Boc) (Scheme 4). Typically, mesylate building blocks 9 were used (X = OMs), which can conveniently be generated from the hydroxyl analog by reacting with MsCl in the presence of a mild base such as Et3N. 1. base, S _N 2 reaction 2. deprotection 8 9 Scheme 4 Alternatively, building blocks of formula 1, where A = N linked heteroaryl, can be prepared by a Mitsunobu type reaction of heterocycle A (8) with a hydroxyl building block 10 (e.g. using diisopropyl azodicarboxylate and triphenylphosphine, or Tsunoda reagent (cyanomethylenetrimethylphosphorane)), followed by deprotection under standard conditions (e.g. with TsOH when PG = Boc). (Scheme 5) Alternatively, building blocks of formula 1 can be prepared by conversion of hydroxyl building block 10 to a mesylate (e.g. using MsCl, Et ₃ N) followed by an SN2 reaction with the heterocycle A (8) in the presence of a base such as NaH. 1. Mitsunobu-type conditions Scheme 5 Alternatively, building blocks of formula 1 where A is a C-linked heteroaryl may be generated using standard heterocyclic synthesis techniques, for example starting from a suitable carboxylic acid (11) or ester, nitrile (12) or diketone (13) derivative. The nitrile derivatives can be generated from the hydroxyl derivatives (10) via conversion to a mesylate (e.g. using MsCl, Et ₃ N) followed by S _N 2 displacement of the mesylate group with cyanide (e.g. using KCN). The diketone derivatives can be generated from the ester derivatives (14). (Scheme 6) Scheme 6 (Hetero)aryl trifluoromethylcyclopropyl building blocks 15 were not generally available, and were instead generated from halide building block 16 (X = I, Br) via Suzuki reaction with 1- (trifluoromethyl)vinylboronic acid to give 17. Cyclopropanation using diphenyl(methyl)sulfonium tetrafluoroborate and LiHMDS gave the required building block 15. (Scheme 7) This sequence could also be carried out inbetween steps in other synthetic schemes, e.g. for N-linked heteroaryl rings A, these functionalization steps could also be carried out while making building blocks of formula 1, after the Chan-Lam coupling/hydrogenation sequence, but prior to final deprotection (see Scheme 3). Alternatively the (hetero)aryl trifluoromethylcyclopropyl building blocks could be generated from commercial building blocks via standard heterocyclic synthesis techniques. Scheme 7 Building blocks of formula 18, where R ₄ = R ₅ = F, can be generated via deoxyfluorination of a suitable ketone 20 (e.g. using DAST, diethylaminosulfur trifluoride), followed by a suitable deprotection (e.g. using TsOH or TFA, where PG = Boc). The ketone can be generated using oxidation of a benzylic CH2 group on a suitable intermediate 19 (generated in Scheme 3), e.g. using SeO ₂ , or alternatively via nucleophilic attack of a metallated-anion derivative of a suitable (hetero)aryl 22 onto a Weinreb amide 23. The intermediate 22 can be generated from a suitable halogenated (hetero)aryl derivate 21 (X = Br, I, Cl) via metallation (e.g. using nBuLi). (Scheme 8) 21 22 Scheme 8 In some cases, where A = fused (hetero)aryl, a suitably substituted mono-cyclic A-ring was introduced as detailled above (e.g. Scheme 3), followed by introduction of the fused (hetero)aryl ring using standard heterocyclic synthesis techniques (e.g. a substituted (hetero)aryl ring A bearing both a ketone and an ortho fluoro group, could be cyclized to a fused oxazole using hydroxylamine hydrochloride.) The introduction of the fused (hetero)aryl typically took place intermediate to the exisiting synthetic steps, most often prior to the deprotection of the building block 1. In some cases, compounds of formula I, could be further functionalized to give other compounds of formula I. For example, a compound of formula I bearing a (hetero)aryl bromide or iodide can be further functionalized with other groups, e.g. an amine, or an alkyl group using metal catalyzed cross-coupling conditions, such as Buchwald or Suzuki reactions. In some cases, building blocks could be generated from commercially available fragments using standard functional group interconversion techniques (e.g. installation of a halide (e.g. using NIS or NBS, removal of a halide (e.g. under hydrogenation conditions), conversion of halides to other groups e.g. small amine, small alkyl using metal catalyzed cross-coupling conditions such as Buchwald or Suzuki reactions, conversion of iodide to a trifluoromethyl group using a trifluoromethylating reagent (e.g. diphenyl(trifluoromethyl)sulfonium trifluoromethanesulfonate), installation and removal of protecting groups, hydrolysis of an ester to an acid, generation of an amide from an acid and a small amine, conversion of boron- containing groups to hydroxyl using alkaline peroxide conditions, cycloaddition of azidotrimethylsilane with a nitrile to generate a tetrazole, Sandmeyer reaction of an aniline to a bromide, oxidation of thioethers to sulfones, oxidation of thioethers to sulfoximines using PhI(OAc)2 and NH2COONH4, alkylation of hydroxyl or amine groups via SN2 reaction or reductive amination, acylation using an activated carbonyl derivative, or installation of –SO2Me or –SO ₂ CF ₃ groups from a iodo- or bromo- building block using literature techniques, installation of small alkyl groups or rings such as cyclopropyl onto heteroaromatic nitrogen using either SN2 alkylation or Chan-Lam type conditions using an alkylboronate, cyclopropanation of an alkene, or installation of a dimethylphosphoryl group in place of a (hetero)aromatic halide (X = Br, I) group via Pd-catalyzed cross-coupling with dimethylphosphine oxide in the presence of a base such as Et3N). Such techniques may also be used to elaborate commercially available fragments before, after, or intermediate within the synthetic sequences described above. In one aspect, the present invention provides a process of manufacturing a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, comprising: (a) reacting an amine of formula 1b, wherein R ¹ , R ² , R ⁴ , R ⁵ , A and B are as described herein, with 6-(1,2,4-triazole-1-carbonyl)-4,4a,5,7,8,8a-hexahydropyrido[ 4,3-b][1,4]oxazin- 3-one (2), in the presence of a base; or (b) reacting 4a,5,6,7,8,8a-hexahydro-4H-pyrido[4,3-b][1,4]oxazin-3-one (2b) with a compound of formula 1c, wherein R ¹ , R ² , R ⁴ , R ⁵ , A and B are as described herein, in the presence of a base, to form said compound of formula (I). In one embodiment, the present invention provides a process of manufacturing a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, comprising: (a) reacting an amine of formula 1, wherein R ¹ , R ² , A and B are as described herein, with 6-(1,2,4-triazole-1-carbonyl)-4,4a,5,7,8,8a-hexahydropyrido[ 4,3-b][1,4]oxazin- 3-one (2), in the presence of a base; or (b) reacting 4a,5,6,7,8,8a-hexahydro-4H-pyrido[4,3-b][1,4]oxazin-3-one (2a) with a compound of formula 1a, wherein R ¹ , R ² , A and B are as described herein, in the presence of a base, to form said compound of formula (I). In one embodiment, said base is DIPEA. In one embodiment, said step (a) or (b) is conducted in a solvent, preferably in DMF or CH3CN. In one embodiment, the amine of formula 1 is obtained by (c) a Suzuki coupling of a compound of formula 6, wherein R ¹ , R ² , and A are as defined herein, and wherein X is bromo or iodo; with a boronate of formula 5, wherein B is as defined herein and R is C1-6-alkyl; in the presence of a base and a palladium catalyst, to form a compound of formula (7), wherein R ¹ , R ² , A and B are as defined herein, and PG is a suitable amino protective group, followed by: (d) hydrogenation of the compound of formula 7 to afford a compound of formula 7a, (e) removal of the amino protective group PG from the compound of formula 7a to afford said compound of formula 1. In one embodiment, said palladium catalyst in step (c) is selected from PdCl(crotyl)(PtBu3) and Pd(dppf)Cl2. In one embodiment, said base in step (c) is K2CO3. In one embodiment, said Suzuki coupling of step (c) is performed in a solvent mixture comprising dioxane and water. In one embodiment, said suitable amino protective group is tert-Butyloxycarbonyl (BOC). In one embodiment, said hydrogenation in step (d) is performed under a hydrogen atmosphere using palladium on charcoal as a catalyst. In one embodiment, said hydrogenation in step (d) is performed under elevated hydrogen pressure, preferably about 22800 mmHg. In one embodiment, said hydrogenation in step (d) is performed in ethyl acetate. In one embodiment, said suitable amino protective group PG is BOC and is removed in step (e) using p-toluenesulfonic acid. In one embodiment, the amine of formula 1 is obtained by (c1) a Mitsunobu-type reaction of an amine of formula 8 with an alcohol of formula 9, wherein PG is a suitable amino protective group in the presence of a phosphine and a dialkyl azodicarboxylate; to form a compound of formula 10, wherein PG is a suitable amino protective group; (d1) removal of the amino protective group PG from the compound of formula 10 to afford said compound of formula 1. In one embodiment, said phosphine is triphenylphosphine. In one embodiment, said dialkyl azodicarboxylate is selected from DEAD and DIAD. In one embodiment, said Mitsunobu-type reaction is conducted in a solvent, preferably in THF. In one embodiment, said suitable amino protective group PG is BOC and is removed in step (d1) using p-toluenesulfonic acid. In one aspect, the present invention provides a compound of formula (I) as described herein, when manufactured according to any one of the processes described herein. MAGL Inhibitory Activity Compounds of the present invention are MAGL inhibitors. Thus, in one aspect, the present invention provides the use of compounds of formula (I) as described herein for inhibiting MAGL in a mammal. In a further aspect, the present invention provides compounds of formula (I) as described herein for use in a method of inhibiting MAGL in a mammal. In a further aspect, the present invention provides the use of compounds of formula (I) as described herein for the preparation of a medicament for inhibiting MAGL in a mammal. In a further aspect, the present invention provides a method for inhibiting MAGL in a mammal, which method comprises administering an effective amount of a compound of formula (I) as described herein to the mammal. Compounds of formula (I) according to the invention were profiled for MAGL inhibitory activity by determining the enzymatic activity by following the hydrolysis of the natural substrate 2-arachidonoylglycerol resulting in arachidonic acid, which can be followed by mass spectrometry. This assay is hereinafter abbreviated “2-AG assay”. The 2-AG assay was carried out in 384 well assay plates (PP, Greiner Cat# 784201) in a total volume of 20 µL. Compound dilutions were made in 100% DMSO (VWR Chemicals 23500.297) in a polypropylene plate in 3-fold dilution steps to give a final concentration range in the assay from 12.5 µM to 0.8 pM.0.25µL compound dilutions (100% DMSO) were added to 9 µL MAGL in assay buffer (50 mM TRIS (GIBCO, 15567-027), 1 mM EDTA (Fluka, 03690- 100ml), 0.01% (v/v) Tween. After shaking, the plate was incubated for 15 min at RT. To start the reaction, 10 µL 2-arachidonoylglycerol in assay buffer was added. The final concentrations in the assay was 50 pM MAGL and 8 µM 2-arachidonoylglyerol. After shaking and 30 min incubation at RT, the reaction was quenched by the addition of 40µL of acetonitrile containing 4µM of d8-arachidonic acid. The amount of arachidonic acid was traced by an online SPE system (Agilent Rapidfire) coupled to a triple quadrupole mass spectrometer (Agilent 6460). A C18 SPE cartridge (G9205A) was used in an acetonitrile/water liquid setup. The mass spectrometer was operated in negative electrospray mode following the mass transitions 303.1 259.1 for arachidonic acid and 311.1 267.0 for d8-arachidonic acid. The activity of the compounds was calculated based on the ratio of intensities [arachidonic acid / d8-arachidonic acid]. Table 1 In one aspect, the present invention provides compounds of formula (I) and their pharmaceutically acceptable salts or esters as described herein, wherein said compounds of formula (I) and their pharmaceutically acceptable salts or esters have IC50’s for MAGL inhibition below 25 µM, preferably below 10 µM, more preferably below 5 µM as measured in the MAGL assays described herein. In one embodiment, compounds of formula (I) and their pharmaceutically acceptable salts or esters as described herein have IC ₅₀ (MAGL inhibition) values between 0.000001 µM and 25 µM, particular compounds have IC ₅₀ values between 0.000005 µM and 10 µM, further particular compounds have IC50 values between 0.00005 µM and 5 µM, as measured in the MAGL assays described herein. P _app (passive permeability measurements) obtained as part of Unidirectional P-gp Screen Experiment Description The general assay uses transfected LLC-PK1 cells (porcine kidney epithelial cells) over- expressing human or mouse P-gp, cultured on 96 well semi-permeable filter membrane plates, where they form a polarized monolayer with tight junctions, and act as a barrier between the apical and basolateral compartment. P-gp is expressed in the apical-facing membrane of the monolayer. The tightness of the cell monolayer and functional activity of P-gp are confirmed by addition of a cell-impermeable marker, Lucifer yellow, and a reference P-gp substrate, edoxaban, respectively. The assay is fully automated on a Tecan liquid handling robot. Data analysis and interpretation For substrate testing the assay determines the unidirectional permeability (P _app A>B Equation 1) of a test compound by dosing to the apical (i.e. donor compartment) side of the cell monolayer, in the absence and presence of specific P-gp inhibitor, zosuquidar, and measuring the movement of the compound into the basolateral (i.e. receiver) compartment over a 3 hour incubation at 37°C. The effect of P-gp is measured by expressing the apical efflux ratio (AP-ER, Equation 2). The mean permeability (P _app ) is determined in the absence of P-gp via the zosuquidar condition. The AP-ER and mean Papp are then used to categorize compound properties for degree of efflux and permeability (Table 2). Equation 1. Papp, A, C0, and dQ/dt represent the apparent permeability, the filter surface area, the initial concentration, and the amount transported per time period, respectively. P _app values are calculated on the basis of a single time point. ^^ ^^ ^^ ^^, ^^ ^^ℎ ( ^^ > ^^) ^^ ^^ − ^^ ^^ = ^^ ^^ ^^ ^^ ( ^^ > ^^) Equation 2. Calculation of the apical efflux ratio (AP-ER). Papp,inh (A>B) is the permeability value in the apical to basolateral direction in the presence of the inhibitor, and Papp (A>B)the permeability value in the apical-to-basolateral direction in the absence of the inhibitor. Results The compounds of the present invention surprisingly exhibit a reduced P _app compared to the compounds disclosed in WO2020104494, while retaining the overall drug-like properties. Thus, the passive permeability of the compounds (Papp) disclosed in WO2020104494 typically came in the 250-350 nm/s range (Table 2), at which point setting up an exposure gradient across tissues becomes extremely challenging. In contrast, the passive permeability of the compounds of the present invention typically come in the 30-250 nm/s range (Table 3), more preferably in the 50- 200 nm/s range which, when in combination with other suitable properties, enables an exposure gradient to be set up across tissues. Table 2 Table 3 Compared with the heteroaryl analogs with L = O disclosed in WO2020104494, a reduction in Papp is also observed due to the novel combination of a heteroaryl group with a CR ⁴ R ⁵ linker, wherein R ⁴ and R ⁵ are as defined herein. Comparing matched pairs Ex.25 of WO2020104494 and present Example 3, P _app is surprsingly reduced from 293 nm/s to 133 nm/s. Using the Compounds of the Invention In one aspect, the present invention provides a compound of formula (I) as described herein for use as therapeutically active substance. In a further aspect, the present invention provides a compound of formula (I) as described herein for use in the treatment or prophylaxis of diseases and disorders that are associated with MAGL. In a further aspect, the present invention provides a method for the treatment or prophylaxis of diseases and disorders that are associated with MAGL, which method comprises administering an effective amount of a compound of formula (I) as described herein to the mammal. In a further aspect, the present invention provides the use of a compound of formula (I) as described herein for the treatment or prophylaxis of diseases and disorders that are associated with MAGL. In a further aspect, the present invention provides the use of a compound of formula (I) as described herein in the preparation of a medicament for the treatment or prophylaxis of diseases and disorders that are associated with MAGL. In one embodiment, said diseases and disorders that are associated with MAGL are selected from neuroinflammation, neurodegenerative diseases, pain, cancer, mental disorders, multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, traumatic brain injury, neurotoxicity, stroke, epilepsy, anxiety, migraine, depression, inflammatory bowel disease, symptoms associated with inflammatory bowel disease, gut motility, visceral pain, fibromyalgia, endometriosis, abdominal pain, abdominal pain associated with irritable bowel syndrome, asthma, COPD, visceral pain, and/or renal disease. In one embodiment, said diseases and disorders that are associated with MAGL are selected from neuroinflammation, neurodegenerative diseases, pain, cancer and/or mental disorders. In one embodiment, said diseases and disorders that are associated with MAGL are selected from multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, traumatic brain injury, neurotoxicity, stroke, epilepsy, anxiety, migraine, depression, inflammatory bowel disease, symptoms associated with inflammatory bowel disease, gut motility, visceral pain, fibromyalgia, endometriosis, abdominal pain, abdominal pain associated with irritable bowel syndrome, asthma, COPD, visceral pain, rheumatoid arthritis, osteoarthritis,pain associated with rheumatoid arthritis, pain associated with osteoarthritis, and/or renal disease. In a preferred embodiment, said diseases and disorders that are associated with MAGL are selected from inflammatory bowel disease, symptoms associated with inflammatory bowel disease, gut motility, visceral pain, fibromyalgia, endometriosis, pain associated with rheumatoid arthritis, pain associated with osteoarthritis, abdominal pain, abdominal pain associated with irritable bowel syndrome, asthma, COPD, visceral pain, and/or renal disease. In a preferred embodiment, said diseases and disorders that are associated with MAGL are selected from inflammatory bowel disease, symptoms associated with inflammatory bowel disease, gut motility, abdominal pain, and/or abdominal pain associated with irritable bowel syndrome. In a preferred embodiment, said diseases and disorders that are associated with MAGL are selected from visceral pain, endometriosis, pain associated with rheumatoid arthritis, and pain associated with osteoarthritis. In a preferred embodiment, said diseases and disorders that are associated with MAGL are selected from endometriosis, pain associated with rheumatoid arthritis, and pain associated with osteoarthritis. In a particularly preferred embodiment, said diseases and disorders that are associated with MAGL are endometriosis. In a particularly preferred embodiment, said diseases and disorders that are associated with MAGL are pain associated with rheumatoid arthritis. In a particularly preferred embodiment, said diseases and disorders that are associated with MAGL are pain associated with osteoarthritis. In a particularly preferred embodiment, said diseases and disorders that are associated with MAGL are inflammatory bowel disease. In a particularly preferred embodiment, said diseases and disorders that are associated with MAGL are symptoms associated with inflammatory bowel disease. In a particularly preferred embodiment, said diseases and disorders that are associated with MAGL are gut motility. In a particularly preferred embodiment, said diseases and disorders that are associated with MAGL are abdominal pain. In a particularly preferred embodiment, said diseases and disorders that are associated with MAGL are abdominal pain associated with irritable bowel syndrome. Pharmaceutical Compositions and Administration In one aspect, the present invention provides a pharmaceutical composition comprising a compound of formula (I) as described herein and a therapeutically inert carrier. The compounds of formula (I) and their pharmaceutically acceptable salts and esters can be used as medicaments (e.g. in the form of pharmaceutical preparations). The pharmaceutical preparations can be administered internally, such as orally (e.g. in the form of tablets, coated tablets, dragées, hard and soft gelatin capsules, solutions, emulsions or suspensions), nasally (e.g. in the form of nasal sprays) or rectally (e.g. in the form of suppositories). However, the administration can also be effected parentally, such as intramuscularly or intravenously (e.g. in the form of injection solutions). The compounds of formula (I) and their pharmaceutically acceptable salts and esters can be processed with pharmaceutically inert, inorganic or organic adjuvants for the production of tablets, coated tablets, dragées and hard gelatin capsules. Lactose, corn starch or derivatives thereof, talc, stearic acid or its salts etc. can be used, for example, as such adjuvants for tablets, dragées and hard gelatin capsules. Suitable adjuvants for soft gelatin capsules are, for example, vegetable oils, waxes, fats, semi- solid substances and liquid polyols, etc. Suitable adjuvants for the production of solutions and syrups are, for example, water, polyols, saccharose, invert sugar, glucose, etc. Suitable adjuvants for injection solutions are, for example, water, alcohols, polyols, glycerol, vegetable oils, etc. Suitable adjuvants for suppositories are, for example, natural or hardened oils, waxes, fats, semi- solid or liquid polyols, etc. Moreover, the pharmaceutical preparations can contain preservatives, solubilizers, viscosity- increasing substances, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, flavorants, salts for varying the osmotic pressure, buffers, masking agents or antioxidants. They can also contain still other therapeutically valuable substances. The dosage can vary in wide limits and will, of course, be fitted to the individual requirements in each particular case. In general, in the case of oral administration a daily dosage of about 0.1 mg to 20 mg per kg body weight, preferably about 0.5 mg to 4 mg per kg body weight (e.g. about 300 mg per person), divided into preferably 1-3 individual doses, which can consist, for example, of the same amounts, should be appropriate. It will, however, be clear that the upper limit given herein can be exceeded when this is shown to be indicated. Tablet Formulation (Wet Granulation) Item Ingredients mg/tablet 1. Compound of formula (I) 5 25 100 500 2. Lactose Anhydrous DTG 125 105 30 150 3. Sta-Rx 1500 6 6 6 30 4. Microcrystalline Cellulose 30 30 30 150 5. Magnesium Stearate 1 1 1 1 Total 167 167 167 831 Manufacturing Procedure 1. Mix items 1, 2, 3 and 4 and granulate with purified water. 2. Dry the granules at 50°C. 3. Pass the granules through suitable milling equipment. 4. Add item 5 and mix for three minutes; compress on a suitable press. Capsule Formulation Item Ingredients mg/capsule 1. Compound of formula (I) 5 25 100 500 2. Hydrous Lactose 159 123 148 --- 3. Corn Starch 25 35 40 70 4. Talc 10 15 10 25 5. Magnesium Stearate 1 2 2 5 Total 200 200 300 600 Manufacturing Procedure 1. Mix items 1, 2 and 3 in a suitable mixer for 30 minutes. 2. Add items 4 and 5 and mix for 3 minutes. 3. Fill into a suitable capsule. Examples The invention will be more fully understood by reference to the following examples. The claims should not, however, be construed as limited to the scope of the examples. In case the preparative examples are obtained as a mixture of enantiomers, the pure enantiomers can be separated by methods described herein or by methods known to the man skilled in the art, such as e.g., chiral chromatography (e.g., chiral SFC) or crystallization. All reaction examples and intermediates were prepared under an argon atmosphere if not specified otherwise. The Examples were generated using a urea coupling between a building block A.X and P.X. Building Blocks A.1 & A.2 could be used interchangeably as free base, or a suitable salt (e.g. hydrochloride, tartrate) as illustrated by the representative Examples below. Example 1 (4aR,8aS)-6-[6-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-2-a zaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one To a solution of (4aR,8aS)-4a,5,6,7,8,8a-hexahydro-4H-pyrido[4,3-b][1,4]oxazi n-6-ium-3- one;(2S,3S)-2,3-bis[(4-methylbenzoyl)oxy]butanedioic acid;(2S,3S)-4-hydroxy-2,3-bis[(4- methylbenzoyl)oxy]-4-oxo-butanoate;hydrate (building block A.1; 56 mg, 0.06 mmol, 1 eq, CAS 2624363-49-9) and DIEA (54 mg, 0.42 mmol, 7 eq) in acetonitrile (1 mL) was added bis(1,2,4-triazol-1-yl)methanone (13 mg, 0.078 mmol, 1.3 eq, CAS 41864-22-6). The reaction mixture was stirred at 30 °C for 2 h. After addition of tosylic acid;6-[[5- (trifluoromethyl)pyrazin-2-yl]methyl]-2-azaspiro[3.3]heptane (building block P.1; 36 mg, 0.06 mmol, 1 eq), stirring was continued at 50 °C overnight. The crude material was purified by preparative HPLC (YMC-Triart C18, 12 nm, 5 µm, 100 x 30 mm, ACN / water+0.1% HCOOH). The product was concentrated in vacuo to afford (4aR,8aS)-6-[6-[[5-(trifluoromethyl)pyrazin-2- yl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a- hexahydropyrido[4,3- b][1,4]oxazin-3-one (11 mg, 100% purity, 41% yield) as colorless gum. MS (ESI): m/z = 440.2 [M+H] ⁺ . Example 12 (4aR,8aS)-6-[6-[[5-(trifluoromethylsulfonyl)-2-pyridyl]methy l]-2-azaspiro[3.3]heptane-2- carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3- one To a solution of (4aR,8aS)-4a,5,6,7,8,8a-hexahydro-4H-pyrido[4,3-b][1,4]oxazi n-3-one (10 mg, 64 µmol, 1 eq, CAS 2377107-31-6) and DIEA (24 mg, 33 uL, 192 µmol, 3 eq) in DMF (500 uL) was added bis(1,2,4-triazol-1-yl)methanone (10 mg, 64 µmol, 1 eq, CAS 41864-22-6). The mixture was stirred at 35 °C for 1 h. DIEA (24 mg, 33 uL, 192 µmol, 3 eq) and tosylic acid;6- [(5-triflyl-2-pyridyl)methyl]-2-azaspiro[3.3]heptane (31 mg, 64 µmol, 1 eq) were added. The reaction mixture was stirred at 70 °C for 15 h. The crude material was purified by preparative HPLC (YMC-Triart C18, 12 nm, 5 µm, 100 x 30 mm, ACN / water+0.1% TEA). The product was concentrated in vacuo afford (4aR,8aS)-6-[6-[(5-triflyl-2-pyridyl)methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one (12 mg, 35%) as white solid. MS (ESI): m/z = 503.2 [M+H] ⁺ . Example 35 (4aR,8aS)-6-[6-[[3-methyl-5-(trifluoromethyl)pyrazol-1-yl]me thyl]-2-azaspiro[3.3]heptane- 2-carbonyl]-4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin- 3-one To a solution of (4aR,8aS)-4a,5,6,7,8,8a-hexahydro-4H-pyrido[4,3-b][1,4]oxazi n-3-one (10 mg, 64 µmol, 1 eq, CAS 2377107-31-6) and DIEA (24 mg, 33 uL, 192 µmol, 3 eq) in DMF (500 uL) was added bis(1,2,4-triazol-1-yl)methanone (10 mg, 64 µmol, 1 eq, CAS 41864-22-6). The mixture was stirred at 35 °C for 1 h. DIEA (24 mg, 33 uL, 192 µmol, 3 eq) and 6-[[3-methyl-5- (trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane ;tosylic acid (27 mg, 64 µmol, 1 eq ) were added. The reaction mixture was stirred at 70 °C for 15 h. The crude material was purified by preparative HPLC (Gemini NX, 12 nm, 5 µm, 100 x 30 mm, ACN / water+0.1% HCOOH). The product was concentrated in vacuo to afford (4aR,8aS)-6-[6-[[3-methyl-5- (trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane -2-carbonyl]-4,4a,5,7,8,8a- hexahydropyrido[4,3-b][1,4]oxazin-3-one (21 mg, 70%) as colorless amorphous oil. MS (ESI): m/z = 442.3 [M+H] ⁺ . Example 113 (4aR,8aS)-6-[6-[[2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin -6-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one To a solution of (4aR,8aS)-4a,5,6,7,8,8a-hexahydro-4H-pyrido[4,3-b][1,4]oxazi n-3- one;hydrochloride (35 mg, 149 µmol, 1 eq, CAS 2411577-59-6) in DMF (836 uL) was added DIEA (134 mg, 181 uL, 1.04 mmol, 7 eq) and bis(1,2,4-triazol-1-yl)methanone (27 mg, 163 µmol, 1.1 eq, CAS 41864-22-6 ). The reaction mixture was stirred at RT for 30 min.6-(2- azaspiro[3.3]heptan-6-ylmethyl)-2-(trifluoromethyl)pyrazolo[ 1,5-a]pyrimidine;2,2,2- trifluoroacetic acid (134 mg, 163 µmol, 1.1 eq) was added. The reaction mixture was stirred at 50 °C for 18 h. The reaction mixture was purified by SFC to give (4aR,8aS)-6-[6-[[2- (trifluoromethyl)pyrazolo[1,5-a]pyrimidin-6-yl]methyl]-2-aza spiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one (62mg, 78% yield) as white solid. MS (ESI): m/z = 479.2 [M+H] ⁺ . Example 114 (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyrid in-6-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one To a solution of (4aR,8aS)-4a,5,6,7,8,8a-hexahydro-4H-pyrido[4,3-b][1,4]oxazi n-3- one;hydrochloride (35 mg, 149 µmol, 1 eq, CAS 2411577-59-6) in DMF (836 uL) was added DIEA (134 mg, 182 uL, 1.04 mmol, 7 eq) and bis(1,2,4-triazol-1-yl)methanone (27 mg, 163 µmol, 1.1 eq, CAS 41864-22-6). The reaction mixture was stirred at RT for 30 min.6-(2- azaspiro[3.3]heptan-6-ylmethyl)-3-(trifluoromethyl)-1H-pyraz olo[3,4-b]pyridine;tosylic acid (105 mg, 163 µmol, 1.1 eq) was added. The reaction mixture was stirred at 50 °C for 18 h. The reaction mixture was purified by reversed-phase HPLC to give (4aR,8aS)-6-[6-[[3- (trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-6-yl]methyl]-2-a zaspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one (37 mg, 49% yield) as white solid. MS (ESI): m/z = 479.2 [M+H] ⁺ . Example 118 (4aR,8aS)-6-[6-[[3-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyrid in-5-yl]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one To a solution of (4aR,8aS)-4a,5,6,7,8,8a-hexahydro-4H-pyrido[4,3-b][1,4]oxazi n-3- one;hydrochloride (35 mg, 149 µmol, 1 eq, CAS 2411577-59-6) in DMF (836 uL) was added DIEA (134 mg, 182 uL, 1.04 mmol, 7 eq) and bis(1,2,4-triazol-1-yl)methanone (27 mg, 163 µmol, 1.1 eq, CAS 41864-22-6). The reaction mixture was stirred at RT for 30 min.5-(2- azaspiro[3.3]heptan-6-ylmethyl)-3-(trifluoromethyl)-1H-pyraz olo[3,4-b]pyridine;tosylic acid (76 mg, 163 µmol, 1.1 eq) was added. The reaction mixture was stirred at 50 °C for 18 h. The reaction mixture was purified by reversed-phase HPLC to give (4aR,8aS)-6-[6-[[3- (trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl]-2-a zaspiro[3.3]heptane-2-carbonyl]- 4,4a,5,7,8,8a-hexahydropyrido[4,3-b][1,4]oxazin-3-one (29 mg, 39% yield as white solid. MS (ESI): m/z = 479.2 [M+H] ⁺ . Example 133 (4aR,8aS)-6-[6-[[6-[1-(trifluoromethyl)cyclopropyl]-3-pyridy l]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one To a solution of (4aR,8aS)-6-[6-[[6-[1-(trifluoromethyl)cyclopropyl]-3-pyridy l]methyl]-2- azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7,8,8a-hexahydropyri do[4,3-b][1,4]oxazin-3-one (85 mg, 180 µmol, 1 eq, CAS 2624363-49-9) in DMF (1 mL) was added DIEA (148 mg, 200 uL, 1.15 mmol, 7 eq) and bis(1,2,4-triazol-1-yl)methanone (29.58 mg, 180 µmol, 1.1 eq, CAS 41864-22-6). The reaction mixture was stirred at RT for 30 min. tosylic acid;6-[[6-[1- (trifluoromethyl)cyclopropyl]-3-pyridyl]methyl]-2-azaspiro[3 .3]heptane (105 mg, 163 µmol, 1 eq) was added. The reaction mixture was stirred at 50 °C for 18 h. The reaction mixture was purified by reversed-phase SFC to give (4aR,8aS)-6-[6-[[6-[1-(trifluoromethyl)cyclopropyl]-3- pyridyl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]-4,4a,5,7, 8,8a-hexahydropyrido[4,3- b][1,4]oxazin-3-one as colorless gum. MS (ESI): m/z = 479.1 [M+H] ⁺ . In analogy to the Examples above, examples in the following table were generated, using the respective building blocks A.X and P.X. Synthesis of Building Blocks Building Blocks A.1 & A.2 Building Blocks A.1 & A.2 are either commercially available or have been reported in the scientific literature e.g. as free base (A.1 free base: CAS 2377107-31-6; A.2 free base: CAS 1821824-68-3), hydrochloride (A.1 HCl: CAS 2411577-59-6; A.2 HCl: CAS 2361608-82-2), or tartrate (A.1 tartrate: CAS 2624363-49-9) salts and could be used interchangeably. In some cases a racemic commercial product was purchased and separated into the respective stereoisomers. (+)-(4aR,8aS)-4a,5,6,7,8,8a-Hexahydro-4H-pyrido[4,3-b][1,4]o xazin-3-one and (-)-(4aS,8aR)-4a,5,6,7,8,8a-Hexahydro-4H-pyrido[4,3-b][1,4]o xazin-3-one A _{.1 (+)} ^{A.2 (-)} The enantiomers of rac-(4aR,8aS)-hexahydro-2H-pyrido[4,3-b][1,4]oxazin-3(4H)-on e dihydrochloride (500 mg, 2.18 mmol, CAS 2629166-65-8, ChemBridge Corporation) were separated by preparative chiral HPLC (ReprosilChiral NR column) using an isocratic mixture of EtOH (containing 0.05% of NH ₄ OAc) : n-heptane (30 : 70). First eluting enantiomer: (+)-(4aR,8aS)-4a,5,6,7,8,8a-Hexahydro-4H-pyrido[4,3-b][1,4]o xazin- 3-one (A.1). Yellow solid (0.150 g; 44.0%). MS (ESI): m/z = 157.1 [M+H] ⁺ . Second eluting enantiomer: (-)-(4aS,8aR)-4a,5,6,7,8,8a-Hexahydro-4H-pyrido[4,3- b][1,4]oxazin-3-one (A.2). Yellow solid (0.152 g; 44.6%). MS (ESI): m/z = 157.1 [M+H] ⁺ . Building Block P.1 : 6-[[5-(Trifluoromethyl)pyrazin-2-yl]methyl]-2-azaspiro[3.3]h eptane; tosylic acid Step 1: tert-butyl 6-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]-2 - azaspiro[3.3]heptane-2-carboxylate A mixture of 2,2,6,6-tetramethylpiperidine (95.9 mL, 568 mmol) in THF (750 mL) was cooled to -30 °C under a N ₂ atmosphere. n-BuLi (227 mL, 568 mmol) was added dropwise, and the reaction mixture was stirred at the same temperature for 30 min. Next, the reaction was cooled to –60 °C, and a solution of 4,4,5,5-tetramethyl-2-[(4,4,5,5-tetramethyl-1,3,2-dioxaborol an-2- yl)methyl]-1,3,2-dioxaborolane (136 g, 506 mmol) in THF (750 mL) was added dropwise. After stirring for 30 min, a solution of tert-butyl 6-oxo-2-azaspiro[3.3]heptane-2-carboxylate (100 g, 473 mmol) in THF (300 mL) was added in dropwise at –60 °C. The reaction mixture was allowed to slowly warm up to 25 °C and stirred at 25 °C for 12 h. The mixture was added H ₂ O (80mL) slowly and then purified together with an additional batch of equal size by silica gel column (PE/EA=1:0 to 3:1 gradient) to give the title compound (220 g, 656 mmol, approx 69% yield per batch) as a white solid which was confirmed by ¹ H NMR (400 MHz, CHLOROFORM- d) δ = 5.21 - 5.16 (m, 1H), 3.99 - 3.89 (m, 4H), 3.13 - 2.90 (m, 4H), 1.46 - 1.41 (m, 9H), 1.26 - 1.20 ppm (m, 13H). Step 2: 6-[[5-(Trifluoromethyl)pyrazin-2-yl]methylene]-2-azaspiro[3. 3]heptane-2-carboxylic acid tert-butyl ester A solution of 6-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]-2 - azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (1 g, 3 mmol, 1 eq, CAS 2763647-64-7), 2-bromo-5-(trifluoromethyl)pyrazine (812 mg, 3.6 mmol, 1.2 eq, CAS 1196152-38-1) and tripotassium phosphate (1.27 g, 6 mmol, 2 eq) in 1,4-dioxane (20 mL), water (2 mL) was degassed with argon. Chloro(crotyl)(tri-tert-butylphosphine)palladium(II) (59 mg, 0.15 mmol, 0.05 eq, CAS 1334497-00-5) was added. The mixture was stirred at 70 °C for 4 h. The reaction mixture was poured into EtOAc and washed with water, NaCl sat. The organic layer was dried over Na ₂ SO ₄ and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 40 g, 0% to 30% EtOAc in heptane) to afford 6-[[5- (trifluoromethyl)pyrazin-2-yl]methylene]-2-azaspiro[3.3]hept ane-2-carboxylic acid tert-butyl ester (593 mg, 97% purity, 54% yield) as white solid. MS (ESI): m/z = [M-C ₄ H ₈ +H] ⁺ . Step 3: 6-[[5-(Trifluoromethyl)pyrazin-2-yl]methyl]-2-azaspiro[3.3]h eptane-2-carboxylic acid tert-butyl ester A solution of 6-[[5-(trifluoromethyl)pyrazin-2-yl]methylene]-2-azaspiro[3. 3]heptane-2- carboxylic acid tert-butyl ester (0.59 g, 1.66 mmol, 1 eq) in tetrahydrofuran (10 mL), methanol (30 mL) was degassed with argon. Pd/C 10% (176 mg, 0.166 mmol, 0.1 eq) was added. The mixture was stirred under H2 balloon at RT for 30 min. The reaction mixture was filtered and concentrated in vacuo to afford 6-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (588 mg, 95% purity, 94% yield) as off- white solid. MS (ESI): m/z = [M-C4H8+H] ⁺ . Step 4: 6-[[5-(Trifluoromethyl)pyrazin-2-yl]methyl]-2-azaspiro[3.3]h eptane; tosylic acid To a solution of 6-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-2-azaspiro[3.3]h eptane-2- carboxylic acid tert-butyl ester (183 mg, 0.51 mmol, 1 eq) in ethyl acetate (1.2 mL) was added 4- methylbenzenesulfonic acid monohydrate (102 mg, 0.54 mmol, 1.05 eq). The mixture was stirred at 80 °C for 16 h. The reaction mixture was concentrated in vacuo to afford 6-[[5- (trifluoromethyl)pyrazin-2-yl]methyl]-2-azaspiro[3.3]heptane ; tosylic acid (228 mg, 94% purity, 98% yield) as light brown solid. MS (ESI): m/z = 258.2 [M+H] ⁺ . In analogy to Building Block P.1, the following building blocks were generated using the relevant (hetero)aryl bromide, chloride or iodide building block for the Suzuki coupling in step 2. In some cases, alternative salts (e.g. trifluoroacetate, ditosylate, hydrochloride) were also used. To introduce different spiro-ring systems alternative building blocks instead of 6-[(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]-2-azaspiro[3. 3]heptane-2-carboxylic acid tert- butyl ester were used in step 2e.g. tert-butyl 7-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)methylene]-2-azaspiro[3.5]nonane-2-carboxylate (CAS 2763648-39-9) for P.84, tert-butyl (6Z)-6-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyle ne]-2-azaspiro[3.4]octane-2- carboxylate (CAS 2763648-54-8) for P.92, or tert-butyl 2-[(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)methylene]-7-azaspiro[3.5]nonane-7-carboxy late (C.184) for P.184. Building Block P.14: [6-(2-Azaspiro[3.3]heptan-6-ylmethyl)-3-pyridyl]-imino-oxo- (trifluoromethyl)-λ⁶-sulfane;4-methylbenzenesulfonic acid Step 1: 2-Bromo-5-(trifluoromethylsulfanyl)pyridine To a solution of 2-bromo-5-iodopyridine (0.5 g, 1.76 mmol, 1 eq) in ACN (10 mL) was added 2,2′-bipyridine (275 mg, 1.76 mmol, 1 eq, CAS 366-18-7), silver (I) trifluoromethanethiolate (441 mg, 2.1 mmol, 1.2 eq, CAS 811-68-7) and CuI (335 mg, 1.76 mmol, 1 eq) at 20 °C. The mixture was stirred at 90 °C for 12 h. The reaction mixture was filtered to afford 2-bromo-5- (trifluoromethylsulfanyl)pyridine (400 mg, 1.55 mmol, 88 % yield). The crude product was directly used in the next step. Step 2: tert-Butyl 6-[[5-(trifluoromethylsulfanyl)-2-pyridyl]methylene]-2-azasp iro[3.3]heptane- 2-carboxylate To a solution of tert-butyl 6-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]-2 - azaspiro[3.3]heptane-2-carboxylate (4.2 g, 12.5 mmol, 1 eq, CAS 2763647-64-7), 2-chloro-5- (trifluoromethylsulfanyl)pyridine (2.67 g, 12.5 mmol, 1 eq, CAS 1204234-94-5) and potassium carbonate (3.46 g, 25 mmol, 2 eq) in 1,4-dioxane (25 mL) and water (5 mL) was added 1,1'- bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (1.02 g, 1.25 mmol, 0.1 eq, CAS 95464-05-4). The mixture was stirred at 80 °C under N ₂ atmosphere for 12 h. The crude material was purified by chromatography on silica gel (heptane/EtOAc 3:1) to afford tert-butyl 6-[[5-(trifluoromethylsulfanyl)-2-pyridyl]methylene]-2-azasp iro[3.3]heptane-2- carboxylate (1.8g, 37% yield) as brown solid. MS (ESI): m/z = 331.0 [M+H] ⁺ . Step 3: tert-Butyl 6-[[5-(trifluoromethylsulfanyl)-2-pyridyl]methyl]-2-azaspiro [3.3]heptane-2- carboxylate To a solution of tert-butyl 6-[[5-(trifluoromethylsulfanyl)-2-pyridyl]methylene]-2- azaspiro[3.3]heptane-2-carboxylate (1.7 g, 4.4 mmol, 1 eq) in EtOAc (20 mL) was added wet Pd/C 10% (1.7 mg, 0.44 mmol, 0.1 eq) at 20 °C under N2, then the mixture was stirred at 20 °C under H2 atmosphere (balloon) for 6 h. The mixture was filtered and concentrated in vacuo to afford tert-butyl 6-[[5-(trifluoromethylsulfanyl)-2-pyridyl]methyl]-2-azaspiro [3.3]heptane-2- carboxylate (1.5 g, 3.86 mmol, 87% yield) as off-white oil. MS (ESI): m/z = [M+H] ⁺ . Step 4: tert-Butyl 6-[[5-(trifluoromethylsulfonimidoyl)-2-pyridyl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[[5-(trifluoromethylsulfanyl)-2-pyridyl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (1 g, 2.57 mmol, 1 eq) in hexafluoroisopropanol (15 mL) was added PhI(OAc)2 (3.48 g, 10.8 mmol, 4.2 eq, CAS 3240-34-4) and ammonium carbamate (602 mg, 7.72 mmol, 3 eq). The reaction mixture was stirred at 20 °C for 12 h and concentrated in vacuo. The residue was purified by prep-HPLC( Phenomenex luna C18150*40mm* 15um, water(FA)-ACN ) and lyophilized to afford tert-butyl 6-[[5-(trifluoromethylsulfonimidoyl)-2- pyridyl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (200 mg, 0.48 mmol, 18% yield) as brown oil. MS (ESI): m/z = 333.0 [M+H] ⁺ . Step 5: [6-(2-Azaspiro[3.3]heptan-6-ylmethyl)-3-pyridyl]-imino-oxo-( trifluoromethyl)-λ6- sulfane;4-methylbenzenesulfonic acid To a solution of tert-butyl 6-[[5-(trifluoromethylsulfonimidoyl)-2-pyridyl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (230 mg, 0.55 mmol, 1 eq) in EtOAc (3 mL) was added p- toluenesulfonic acid (113 mg, 0.66 mmol, 1.2 eq). The mixture was stirred at 80 °C for 12 h. The reaction mixture was concentrated in vacuo, then deionized water was added and lyophilized to afford [6-(2-azaspiro[3.3]heptan-6-ylmethyl)-3-pyridyl]-imino-oxo-( trifluoromethyl)-λ6- sulfane;4-methylbenzenesulfonic acid (244 mg, 0.5 mmol, 85% yield) as brown solid. MS (ESI): m/z = 320.0 [M+H] ⁺ . In analogy to Building Block P.14, the following building blocks were generated using the relevant (hetero)aryl bromo or iodo compound for the cross coupling reaction in Step 1. Building Block P.15: 2-(2-Azaspiro[3.3]heptan-6-ylmethyl)-5-[1- (trifluoromethyl)cyclopropyl]-1,3,4-oxadiazole;4-methylbenze nesulfonic acid Step 1: 6-(2-Hydrazino-2-keto-ethyl)-2-azaspiro[3.3]heptane-2-carbox ylic acid tert-butyl ester To a solution of 2-(2-tert-butoxycarbonyl-2-azaspiro[3.3]heptan-6-yl)acetic acid (2.5 g, 9.8 mmol, 1 eq, CAS 1251002-39-7) in tetrahydrofuran (30 mL) was added CDI (1.75 g, 10.7 mmol, 1 eq). The mixture was stirred at 70 °C for 1.5 h and cooled to 0 °C. Hydrazine monohydrate (1.47 g, 29.4 mmol, 3 eq) was added. The mixture was stirred at RT for 30 min. The reaction mixture was poured into EtOAc/THF 2:1, washed with H2O, NaCl sat., dried over Na2SO4 and concentrated in vacuo to afford 6-(2-hydrazino-2-keto-ethyl)-2-azaspiro[3.3]heptane-2- carboxylic acid tert-butyl ester (3.85 g, 68% purity, 99% yield) as white solid. MS (ESI): m/z = 214.1 [M-C ₄ H ₈ +H] ⁺ . Step 2: 6-[2-Keto-2-[N'-[1-(trifluoromethyl)cyclopropanecarbonyl]hyd razino]ethyl]-2- azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester To a solution of 1-(trifluoromethyl)cyclopropanecarboxylic acid (1.5 g, 9.7 mmol, 1 eq, CAS 277756-46-4) in dichloromethane (30 mL) was added 1-chloro-N,N,2-trimethylpropenylamine (1.56 g, 11.6 mmol, 1.2 eq, CAS 26189-59-3). The mixture was stirred at RT for 2 h. This carboxylic acid chloride solution was added dropwise to a solution of 6-(2-hydrazino-2-keto- ethyl)-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (3.85 g, 9.7 mmol, 1 eq) and DIPEA (2.51 g, 19.4 mmol, 2 eq) in tetrahydrofuran (20 mL) at RT. The mixture was stirred at RT for 2 h. The reaction mixture was poured into EtOAc/THF 2:1 and washed with water, NaCl sat. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 80g, 0% to 5% methanol in CH2Cl2) to afford 6- [2-keto-2-[N'-[1-(trifluoromethyl)cyclopropanecarbonyl]hydra zino]ethyl]-2- azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (3.49 g, 95% purity, 84%yield) as white solid. MS (ESI): m/z = 350.1 [M-C4H8+H] ⁺ . Step 3: 6-[[5-[1-(Trifluoromethyl)cyclopropyl]-1,3,4-oxadiazol-2-yl] methyl]-2- azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester To a solution of 6-[2-keto-2-[N'-[1-(trifluoromethyl)cyclopropanecarbonyl]hyd razino]ethyl]-2- azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (3.49 g, 8.61 mmol, 1 eq) in tetrahydrofuran (40 mL) was added Burgess reagent (4.1 g, 17.2 mmol, 2 eq, CAS 29684-56-8). The mixture was stirred at 60 °C for 1 h. The reaction mixture was poured into EtOAc/THF 3:1 and washed with water, NaCl sat. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 80 g, 0% to 5% methanol in CH2Cl2) to afford 6-[[5-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazol-2- yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (3.22 g, 95% purity, 91% yield) as white solid. MS (ESI): m/z = 388.2 [M+H] ⁺ . Step 4: 2-(2-Azaspiro[3.3]heptan-6-ylmethyl)-5-[1-(trifluoromethyl)c yclopropyl]-1,3,4- oxadiazole;4-methylbenzenesulfonic acid To a solution of 6-[[5-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazol-2-yl] methyl]-2- azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (3.22 g, 8.31 mmol, 1 eq) in isopropyl acetate (160 mL) was added p-toluenesulfonic acid monohydrate (1.9 g, 9.97 mmol, 1.2 eq). The mixture was stirred at 85 °C for 4 h and concentrated in vacuo to afford 2-(2- azaspiro[3.3]heptan-6-ylmethyl)-5-[1-(trifluoromethyl)cyclop ropyl]-1,3,4-oxadiazole;4- methylbenzenesulfonic acid (4.25 g, 40% purity, 44% yield) as white solid. MS (ESI): m/z = 288.0 [M+H] ⁺ . Building Block P.16: 4-Methylbenzenesulfonic acid;6-[[3-[1-(trifluoromethyl)cyclopropyl]- 1,2,4-triazol-1-yl]methyl]-2-azaspiro[3.3]heptane Step 1: tert-Butyl 6-[(3-bromo-1,2,4-triazol-1-yl)methylene]-2-azaspiro[3.3]hep tane-2- carboxylate To a solution of 3-bromo-1H-1,2,4-triazole (2 g, 13.5 mmol, 1 eq, CAS 7343-33-1) in DCE (40 mL) were added tert-butyl 6-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]-2 - azaspiro[3.3]heptane-2-carboxylate (6.8 g, 20.2 mmol, 1.5 eq, CAS 2763647-64-7), pyridine (2.2 mL, 27 mmol, 2 eq), boric acid (835 mg, 13.5 mmol, 1 eq) and Cu(OAc) ₂ (3.64 g, 18.2 mmol, 1.35 eq). The mixture was stirred at 70 °C for 12 h. The reaction mixture was poured into EtOAc and washed with water, NaCl sat. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 12 g, 0% to 50% EtOAc in heptane) to afford tert-butyl 6-[(3-bromo-1,2,4-triazol-1-yl)methylene]- 2-azaspiro[3.3]heptane-2-carboxylate (1.7 g, 35% yield) as yellow solid. MS (ESI): m/z = 354.9 [M+H] ⁺ . Step 2: tert-Butyl 6-[[3-[1-(trifluoromethyl)vinyl]-1,2,4-triazol-1-yl]methyl]- 2- azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[(3-bromo-1,2,4-triazol-1-yl)methylene]-2-azaspiro[3.3]hep tane-2- carboxylate (500 mg, 1.4 mmol, 1 eq) in THF (5 mL) was added 4,4,6-trimethyl-2-[1- (trifluoromethyl)vinyl]-1,3,2-dioxaborinane (374 mg, 1.7 mmol, 1.2 eq, CAS 1011460-68-6), K3PO41.5 M aq. (2.8 mL, 4.2 mmol, 3 eq) and Ad2nBuP-Pd-G3 (162 mg, 0.14 mmol, 0.1 eq, CAS 1651823-59-4). The mixture was stirred at 100 °C for 16 h and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 0% to 45% EtOAc in heptane) to afford tert-butyl 6-[[3-[1-(trifluoromethyl)vinyl]-1,2,4-triazol-1-yl]methyl]- 2- azaspiro[3.3]heptane-2-carboxylate (450 mg, 85% yield) as off-white solid. MS (ESI): m/z = 317.1 [M-C4H8+H] ⁺ . Step 3: tert-Butyl 6-[[3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-triazol-1-yl]me thyl]-2- azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[[3-[1-(trifluoromethyl)vinyl]-1,2,4-triazol-1-yl]methyl]- 2- azaspiro[3.3]heptane-2-carboxylate (1.1 g, 3 mmol, 1 eq) in THF (11 mL) was added diphenyl(methyl)sulfonium tetrafluoroborate (851 mg, 3 mmol, 1 eq, CAS 10504-60-6). The suspension was cooled to 0 °C and NaHMDS 1M in THF (4.7 mL, 4.7 mmol, 1.6 eq) was added dropwise. The reaction mixture was stirred at 20 °C for 12 h. The crude product was purified by prep-HPLC (Shim-pack C18150*25*10um, water(0.225%FA)-ACN) to afford tert-butyl 6-[[3- [1-(trifluoromethyl)cyclopropyl]-1,2,4-triazol-1-yl]methyl]- 2-azaspiro[3.3]heptane-2- carboxylate (440 mg, 1.14 mmol, 38% yield). MS (ESI): m/z = [M-C ₄ H ₈ +H] ⁺ . Step 4: 4-Methylbenzenesulfonic acid;6-[[3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-triazol-1- yl]methyl]-2-azaspiro[3.3]heptane A solution of p-toluenesulfonic acid (256 mg, 1.5 mmol, 1.2 eq) and tert-butyl 6-[[3-[1- (trifluoromethyl)cyclopropyl]-1,2,4-triazol-1-yl]methyl]-2-a zaspiro[3.3]heptane-2-carboxylate (480 mg, 1.24 mmol, 1 eq) in EtOAc (5 mL) was stirred at 80 °C for 12 h. The mixture was concentrated in vacuo. To the residue was added deionized water and lyophilized to afford 4- methylbenzenesulfonic acid;6-[[3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-triazol-1- yl]methyl]-2- azaspiro[3.3]heptane (551 mg, 96% yield) as a yellow oil. MS (ESI): m/z = 287.0 [M+H] ⁺ . In analogy to Building Block P.16, the following building block was generated using the relevant heteroaryl compound for the Chan Lam-type coupling in Step 1. Building Block P.19: 4-methylbenzenesulfonic acid;6-[[4-[1- (trifluoromethyl)cyclopropyl]imidazol-1-yl]methyl]-2-azaspir o[3.3]heptane To a solution of tert-butyl 6-[[4-[1-(trifluoromethyl)cyclopropyl]imidazol-1-yl]methyl]- 2- azaspiro[3.3]heptane-2-carboxylate (700 mg, 1.82 mmol, 1 eq) in EtOAc (14 mL) was added p- toluenesulfonic acid monohydrate (1036 mg, 5.45 mmol, 3 eq). The reaction mixture was stirred at 30 °C for 72 h, concentrated in vacuo and purified by FC to give 4-methylbenzenesulfonic acid;6-[[4-[1-(trifluoromethyl)cyclopropyl]imidazol-1-yl]met hyl]-2-azaspiro[3.3]heptane (563 mg, 0.89 mmol, 46% yield) as yellow solid. MS (ESI): m/z = 286.2 [M+H] ⁺ . FC conditions: Interchim, 80 g SiO2, MTBE / methanol (0-66-100%), flow rate = 60 ml/min, 13,8-14,9 CV. Step 1: tert-butyl 6-[(4-bromoimidazol-1-yl)methyl]-2-azaspiro[3.3]heptane-2-ca rboxylate To a solution of 4-bromo-1H-imidazole (1443, mg, 9.82 mmol, 1.5 eq, CAS 2302-25-2) in NMP (20 mL) was added NaH (471 mg, 11.79 mmol, 1.8 eq) at 0 °C under nitrogen. The resulting yellow solution was stirred at 0 °C for 30 min. tert-Butyl 6- (methylsulfonyloxymethyl)-2-azaspiro[3.3]heptane-2-carboxyla te (2 g, 6.55 mmol, 1 eq, CAS 2740574-92-7) was added and stirred at 50 °C for 12 h. The mixture was diluted with 20 ml saturated NH ₄ Cl aqueous solution, extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo. The residue was purified by reverse-HPLC (0.01% FA in water:ACN=100% to 0%,220&254nm) and lyophilized to give tert-butyl 6-[(4-bromoimidazol-1-yl)methyl]-2-azaspiro[3.3]heptane-2-ca rboxylate (1.1 g, 3.09 mmol, 47% yield) as yellow solid. MS (ESI): m/z = 358.1 [M+H] ⁺ . To a solution of tert-butyl 6-[(4-bromoimidazol-1-yl)methyl]-2-azaspiro[3.3]heptane-2- carboxylate (5 g, 14.03 mmol, 1 eq) and 4,4,6-trimethyl-2-[1-(trifluoromethyl)vinyl]-1,3,2- dioxaborinane (3.74 g, 16.84 mmol, 1.2 eq, CAS 1011460-68-6), K3PO4 (8.93 g, 42.1 mmol, 3 eq) in THF (165 mL) and water (33 mL) was added APhos-Pd-G3 (891.35 mg, 1.4 mmol, 0.1 eq, CAS 1820817-64-8). The mixture was degassed with N ₂ and stirred at 60 °C under N ₂ atmosphere for 12 h. The crude material was purified by column on silica (petroleum ether:ethyl acetate=1:1~0:1) and concentrated in vacuo to give tert-butyl 6-[[4-[1- (trifluoromethyl)vinyl]imidazol-1-yl]methyl]-2-azaspiro[3.3] heptane-2-carboxylate (3.2 g, 8.62 mmol, 61% yield) as yellow oil. MS (ESI): m/z = 372.2 [M+H] ⁺ . Step 3: tert-butyl 6-[[4-[1-(trifluoromethyl)cyclopropyl]imidazol-1-yl]methyl]- 2- azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[[4-[1-(trifluoromethyl)vinyl]imidazol-1-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (2 g, 5.39 mmol, 1 eq) in THF (40 mL) was added diphenyl(methyl)sulfonium tetrafluoroborate (1.86 g, 6.46 mmol, 1.2 eq, CAS 10504-60-6) at 20 °C. The suspension was cooled to 0 °C and NaHMDS/THF (8.62 mL, 8.62 mmol, 1.6 eq) was added dropwise under N2. The reaction mixture was stirred at RT for 12 h. The reaction mixture was poured into saturated NH4Cl aqueous solution and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO ₂ , petroleum ether:ethyl acetate=.0:1 ) to give a crude. The crude product was purified by prep-HPLC (Column, [Phenomenex luna C18150*40mm* 15um]; mobile phase: [ACN] and [H2O] (conditions: [water(0.225%FA)-ACN], B%: 50%-80%; Detector, UV 254 nm. RT: [15 min]) and lyophilized to give tert-butyl 6-[[4-[1- (trifluoromethyl)cyclopropyl]imidazol-1-yl]methyl]-2-azaspir o[3.3]heptane-2-carboxylate (644 mg, 1.67 mmol, 31% yield) as yellow oil. MS (ESI): m/z = 386.2 [M+H] ⁺ . Building Block P.23: 1-(2-Azaspiro[3.3]heptan-6-ylmethyl)-4-(trifluoromethyl)pyri din-2- one;4-methylbenzenesulfonic acid Step1: tert-Butyl 6-[[2-oxo-4-(trifluoromethyl)-1-pyridyl]methyl]-2-azaspiro[3 .3]heptane-2- carboxylate 4-(Trifluoromethyl)-1H-pyridin-2-one (5.34 g, 32.75 mmol, 1 eq, CAS 50650-59-4) was added in small portions under argon at 0 °C to a suspension of sodium hydride 60% in oil (2.14 g, 49.1 mmol, 1.5 eq) in DMF (100 mL). The mixture was stirred at 0 °C for 10 minutes and at room temperature for 30 minutes. The reaction mixture was cooled to 0 °C and tert-butyl 6- (methylsulfonyloxymethyl)-2-azaspiro[3.3]heptane-2-carboxyla te (10 g, 32.7 mmol, 1 eq, CAS 2740574-92-7), sodium iodide (4.91 g, 32.7 mmol, 1 eq) were added. The mixture was stirred at 0 °C for 1 h then at 80 °C for 18 h. The reaction mixture was poured into EtOAc and washed with water, NaCl sat. The organic layer was dried over Na ₂ SO ₄ and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 120 g, 0% to 100% tert- butylmethylether in heptane) to afford tert-butyl 6-[[2-oxo-4-(trifluoromethyl)-1- pyridyl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (3.6 g, 29% yield) as yellow solid. MS (ESI): m/z = 273.0 [M+H] ⁺ . Step 2: 1-(2-Azaspiro[3.3]heptan-6-ylmethyl)-4-(trifluoromethyl)pyri din-2-one;4- methylbenzenesulfonic acid To a solution of tert-butyl 6-[[2-oxo-4-(trifluoromethyl)-1-pyridyl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (5 g, 13.43 mmol, 1 eq) in ethyl acetate (150 mL) was added p-toluenesulfonic acid monohydrate (5.1 g, 26.8 mmol, 2 eq) and stirred at 25 °C for 72 h. The reaction mixture was filtered and washed with diethyl ether to afford 1-(2-azaspiro[3.3]heptan-6- ylmethyl)-4-(trifluoromethyl)pyridin-2-one;4-methylbenzenesu lfonic acid (5.34 mg, 85% yield) as light yellow solid. MS (ESI): m/z = 273.0 [M+H] ⁺ . Building Block P.24: 1-(2-Azaspiro[3.3]heptan-6-ylmethyl)-5-(trifluoromethyl)pyri din-2- one;4-methylbenzenesulfonic acid By analogy with Building Block P.23, 5-(trifluoromethyl)-1H-pyridin-2-one (CAS 33252-63-0) was treated with sodium hydride, tert-butyl 6-(methylsulfonyloxymethyl)-2- azaspiro[3.3]heptane-2-carboxylate CAS 2740574-92-7 and sodium iodide in DMF. The resulting product was treated with p-toluenesulfonic acid monohydrate to afford 1-(2- azaspiro[3.3]heptan-6-ylmethyl)-5-(trifluoromethyl)pyridin-2 -one;4-methylbenzenesulfonic acid as white solid. MS (ESI): m/z = 273.0 [M+H] ⁺ . Building Block P.33: 4-Methylbenzenesulfonic acid;6-[[4-(2,2,2-trifluoroethyl)pyrazol-1- yl]methyl]-2-azaspiro[3.3]heptane Step 1: tert-Butyl 6-[[4-(2,2,2-trifluoroethyl)pyrazol-1-yl]methyl]-2-azaspiro[ 3.3]heptane-2- carboxylate To a mixture of 4-(2,2,2-trifluoroethyl)-1H-pyrazole (737 mg, 4.9 mmol, 1 eq, CAS 1211529- 61-1), sodium iodide (1.47 g, 9.8 mmol, 2 eq) and cesium carbonate (3.2 g, 9.8 mmol, 2 eq) in acetonitrile (68 mL) was added tert-butyl 6-(methylsulfonyloxymethyl)-2-azaspiro[3.3]heptane- 2-carboxylate (1.5 g, 4.9 mmol, 1 eq, CAS 2740574-92-7) at room temperature. The reaction mixture was stirred at 80 °C for 18 h, filtered and concentrated in vacuo. The crude material was purified by HPLC to afford tert-butyl 6-[[4-(2,2,2-trifluoroethyl)pyrazol-1-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (223 mg, 12% yield) as light yellow solid. MS (ESI): m/z = 360 [M+H] ⁺ . Step 2: 4-Methylbenzenesulfonic acid;6-[[4-(2,2,2-trifluoroethyl)pyrazol-1-yl]methyl]-2- azaspiro[3.3]heptane To a solution of tert-butyl 6-[[4-(2,2,2-trifluoroethyl)pyrazol-1-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (250 mg, 0.7 mmol, 1 eq) in EtOAc (7.5 mL) was added p- toluenesulfonic acid monohydrate (330 mg, 1.74 mmol, 2.5 eq) and stirred at 25 °C for 18 h. The reaction mixture was concentrated in vacuo and purified by HPLC to afford 4- methylbenzenesulfonic acid;6-[[4-(2,2,2-trifluoroethyl)pyrazol-1-yl]methyl]-2- azaspiro[3.3]heptane (198 mg, 0.46 mmol, 62% yield) as light brown gum. MS (ESI): m/z = 260 [M+H] ⁺ . Building Blocks P.35 & P.36: 4-Methylbenzenesulfonic acid;6-[[3-methyl-5-(trifluoromethyl)pyrazol-1-yl]methyl]-2- azaspiro[3.3]heptane (P.35) 4-Methylbenzenesulfonic acid;6-[[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]methyl]-2- azaspiro[3.3]heptane (P.36) Step 1: tert-Butyl 6-[[3-methyl-5-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azasp iro[3.3]heptane- 2-carboxylate and tert-butyl 6-[[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azasp iro[3.3]heptane-2- carboxylate To a solution of tert-butyl 6-(hydroxymethyl)-2-azaspiro[3.3]heptane-2-carboxylate (6 g, 26.4 mmol, 1 eq, CAS 1363381-93-4), triphenylphosphine (8.65 g, 33 mmol, 1.25 eq) and 5-methyl- 3-(trifluoromethyl)-1H-pyrazole (3.96 g, 26.4 mmol, 1 eq) in THF (120 mL), diisopropyl azodicarboxylate (6.24 mL, 31.7 mmol, 1.2 eq) was added dropwise. The mixture was stirred at room temperature for 24 h. The reaction mixture was concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 330 g, 0% to 35% MTBE in heptane) to afford tert-butyl 6-[[3-methyl-5-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azasp iro[3.3]heptane-2- carboxylate (2.3 g, 24% yield) as white solid. MS (ESI): m/z = 360.0 [M+H] ⁺ and tert-butyl 6-[[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azasp iro[3.3]heptane-2- carboxylate (3.8 g, 40% yield) as colorless oil. MS (ESI): m/z = 360.0 [M+H] ⁺ . Step 2: 4-Methylbenzenesulfonic acid;6-[[3-methyl-5-(trifluoromethyl)pyrazol-1-yl]methyl]-2- azaspiro[3.3]heptane (P.35) To a solution of tert-butyl 6-[[3-methyl-5-(trifluoromethyl)pyrazol-1-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (1.05 g, 2.9 mmol, 1 eq) in EtOAc (10 mL) was added p- toluenesulfonic acid monohydrate (603 mg, 3.51 mmol, 1.2 eq). The mixture was stirred at 80 °C for 12 h. The reaction mixture was concentrated in vacuo and lyophilized to afford 4- methylbenzenesulfonic acid;6-[[3-methyl-5-(trifluoromethyl)pyrazol-1-yl]methyl]-2- azaspiro[3.3]heptane (1.16 g, 89% yield) as light brown powder. MS (ESI): m/z = 260.0 [M+H] ⁺ . Step 2: 4-Methylbenzenesulfonic acid;6-[[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]methyl]-2- azaspiro[3.3]heptane (P.36) To a solution of tert-butyl 6-[[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (700 mg, 1.95 mmol, 1 eq) in EtOAc (7 mL) was added p- toluenesulfonic acid monohydrate (402 mg, 2.34 mmol, 1.2 eq). The mixture was stirred at 80 °C for 2.5 h. The reaction mixture was concentrated in vacuo and lyophilized to afford 4- methylbenzenesulfonic acid;6-[[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]methyl]-2- azaspiro[3.3]heptane (840 mg, 97% yield) as light brown powder. MS (ESI): m/z = 260.0 [M+H] ⁺ . Building Block P.47: 5-(2-Azaspiro[3.3]heptan-6-ylmethyl)-3-(trifluoromethyl)-1,2 ,4- oxadiazole;4-methylbenzenesulfonic acid Step 1: tert-Butyl 6-[[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]methyl]-2-azasp iro[3.3]heptane- 2-carboxylate To a solution of tert-butyl 6-(2-ethoxy-2-oxo-ethyl)-2-azaspiro[3.3]heptane-2-carboxylat e (300 mg, 1.06 mmol, 1 eq, CAS 2122433-35-4) in methanol (3 mL) was added sodium methoxide 5 M (0.42 mL, 2.1 mmol, 2 eq) and 2,2,2-trifluoro-N'-hydroxy-acetamidine (271 mg, 2.1 mmol, 2 eq, CAS 4314-35-6). The mixture was stirred at 60 °C for 12 h. The reaction mixture concentrated in vacuo, dissolved in EtOAc and washed with water. The residue was purified by prep-HPLC (Shim-pack C18150*25*10um,water(FA)-ACN,25ml/min) and lyophilized to afford tert-butyl 6-[[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]methyl]-2-azasp iro[3.3]heptane-2- carboxylate (120 mg, 32% yield) as yellow oil. MS (ESI): m/z = 292.0 [M-C4H8+H] ⁺ . Step 2: 5-(2-Azaspiro[3.3]heptan-6-ylmethyl)-3-(trifluoromethyl)-1,2 ,4-oxadiazole;4- methylbenzenesulfonic acid To a solution of tert-butyl 6-[[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (118 mg, 0.34 mmol, 1 eq) in EtOAc (2 mL) was added p- toluenesulfonic acid (70 mg, 0.41 mmol, 1.2 eq). The reaction mixture was stirred at 80 °C for 12 h and concentrated in vacuo. To the residue was added deionized water and lyophilized to afford 5-(2-azaspiro[3.3]heptan-6-ylmethyl)-3-(trifluoromethyl)-1,2 ,4-oxadiazole;4- methylbenzenesulfonic acid (125 mg, 0.3 mmol, 84% yield) as white solid. MS (ESI): m/z = 248.1 [M+H] ⁺ . Building Block P.48: 3-(2-Azaspiro[3.3]heptan-6-ylmethyl)-5-(trifluoromethyl)-1,2 ,4- oxadiazole;4-methylbenzenesulfonic acid Step 1: tert-Butyl 6-[(2Z)-2-amino-2-hydroxyimino-ethyl]-2-azaspiro[3.3]heptane -2-carboxylate To a mixture of hydroxylamine;hydrochloride (2.35 g, 33.8 mmol, 2 eq) in ethanol (25 mL) was added TEA (3.42 g, 33.8 mmol, 2 eq) at 25 °C. After 1 h, tert-butyl 6-(cyanomethyl)-2- azaspiro[3.3]heptane-2-carboxylate (4 g, 16.9 mmol, 1 eq, CAS 1374658-94-2) was added. The mixture was stirred at 50 °C for 12 h. The reaction mixture concentrated in vacuo, dissolved in EtOAc and washed with water. The organic layer was dried over Na2SO4 and concentrated in vacuo to afford tert-butyl 6-[(2Z)-2-amino-2-hydroxyimino-ethyl]-2-azaspiro[3.3]heptane -2- carboxylate (4.5 g, 98% yield) as colorless oil. MS (ESI): m/z = 270.1 [M+H] ⁺ . Step 2: tert-Butyl 6-[[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]methyl]-2-azasp iro[3.3]heptane- 2-carboxylate To a solution of tert-butyl 6-[(2Z)-2-amino-2-hydroxyimino-ethyl]-2-azaspiro[3.3]heptane -2- carboxylate (800 mg, 2.97 mmol, 1 eq) in methanol (20 mL) was added sodium methoxide 5 M (1.19 mL, 5.94 mmol, 2 eq) and ethyl trifluoroacetate (2.11 g, 14.85 mmol, 5 eq) at 30 °C. The mixture was stirred at 50 °C for 12 h. The reaction mixture concentrated in vacuo, dissolved in EtOAc and washed with water. The residue was purified by prep-HPLC (Shim-pack C18 150*25*10um,water(FA)-ACN,25ml/min) and lyophilized to afford tert-butyl 6-[[5- (trifluoromethyl)-1,2,4-oxadiazol-3-yl]methyl]-2-azaspiro[3. 3]heptane-2-carboxylate (360 mg, 36% yield) as colorless oil. MS (ESI): m/z = 292.0 [M+H] ⁺ . Step 3: 3-(2-Azaspiro[3.3]heptan-6-ylmethyl)-5-(trifluoromethyl)-1,2 ,4-oxadiazole;4- methylbenzenesulfonic acid A mixture of tert-butyl 6-[[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (350 mg, 1 mmol, 1 eq) and p-toluenesulfonic acid (208 mg, 1.2 mmol, 1.2 eq) in EtOAc (10 mL) was stirred at 80 °C for 12 h. The reaction mixture was concentrated in vacuo. The residue was dissolved in ACN (2 mL), water (20 mL) and lyophilized to afford 3-(2-azaspiro[3.3]heptan-6-ylmethyl)-5- (trifluoromethyl)-1,2,4-oxadiazole;4-methylbenzenesulfonic acid (410 mg, 90% yield) as white solid. MS (ESI): m/z = 248.0 [M+H] ⁺ . Building Block P.50: 4-Methylbenzenesulfonic acid;6-[[4-(trifluoromethyl)triazol-2- yl]methyl]-2-azaspiro[3.3]heptane Step 1: tert-Butyl 6-[[4-(trifluoromethyl)triazol-2-yl]methyl]-2-azaspiro[3.3]h eptane-2- carboxylate To a mixture of 4-(trifluoromethyl)-1H-triazole (2.69 g, 19.65 mmol, 1 eq, CAS 1267573-04-5), lithium bromide (3.41 g, 39.3 mmol, 2 eq) in acetonitrile (300 mL) was added tert-butyl 6- (methylsulfonyloxymethyl)-2-azaspiro[3.3]heptane-2-carboxyla te (6 g, 19.65 mmol, 1 eq, CAS 2740574-92-7). The reaction mixture was stirred at 50 °C for 18 h, filtered and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 220 g, 0% to 100% MTBE in heptane) to afford tert-butyl 6-[[4-(trifluoromethyl)triazol-2-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (2.5 g, 36% yield) as light yellow solid. MS (ESI): m/z = 247.0 [M-C ₄ H ₈ +H] ⁺ . Step 2: 4-Methylbenzenesulfonic acid;6-[[4-(trifluoromethyl)triazol-2-yl]methyl]-2- azaspiro[3.3]heptane To a solution of tert-butyl 6-[[4-(trifluoromethyl)triazol-2-yl]methyl]-2-azaspiro[3.3]h eptane-2- carboxylate (2.5 g, 7.2 mmol, 1 eq) in EtOAc (100 mL) was added p-toluenesulfonic acid monohydrate (4.12 g, 21.6 mmol, 3 eq). The reaction mixture was stirred at 25 °C for 18 h, filtered and washed with diethyl ether to afford 4-methylbenzenesulfonic acid;6-[[4- (trifluoromethyl)triazol-2-yl]methyl]-2-azaspiro[3.3]heptane (3.63 g, 81% yield) as white powder. MS (ESI): m/z = 247.2 [M+H] ⁺ . During the synthesis of Building Block P.50 regioisomeric compound tert-butyl 6-[[4- (trifluoromethyl)triazol-1-yl]methyl]-2-azaspiro[3.3]heptane -2-carboxylate was formed in step 1 as minor byproduct which was subsequently converted to the 4- methylbenzenesulfonic acid salt of 6-[[4-(trifluoromethyl)triazol-1-yl]methyl]-2- azaspiro[3.3]heptane following the procedure described in step 2 of Building Block P.50 synthesis. Building Block P.51: 4-Methylbenzenesulfonic acid;6-[[5-(trifluoromethyl)-1,2,4-triazol-1- yl]methyl]-2-azaspiro[3.3]heptane Step 1: 4-Methylbenzenesulfonic acid;6-[[5-(trifluoromethyl)-1,2,4-triazol-1-yl]methyl]-2- azaspiro[3.3]heptane To a solution of 3-(trifluoromethyl)-1H-1,2,4-triazole (417 mg, 3 mmol, 1.5 eq, CAS 60406-75- 9) in NMP (6 mL) was added sodium hydride 60% in oil (146 mg, 3.65 mmol, 1.8 eq) at 0 °C. The mixture was stirred at 0 °C for 0.5 h. tert-Butyl 6-(methylsulfonyloxymethyl)-2- azaspiro[3.3]heptane-2-carboxylate (620 mg, 2 mmol, 1 eq, CAS 2740574-92-7) was added at 20 °C. The reaction mixture was stirred at 50 °C for 12 h. The crude product was purified by HPLC（Welch Ultimate XB-SiOH 250*50*10um，Hexane-EtOH) and concentrated in vacuo to afford 4-methylbenzenesulfonic acid;6-[[5-(trifluoromethyl)-1,2,4-triazol-1-yl]methyl]-2- azaspiro[3.3]heptane (55 mg, 8% yield) as light yellow oil. MS (ESI): m/z = 291.1 [M- C4H8+H] ⁺ . Step 2: 4-Methylbenzenesulfonic acid;6-[[5-(trifluoromethyl)-1,2,4-triazol-1-yl]methyl]-2- azaspiro[3.3]heptane To a solution of tert-butyl 6-[[5-(trifluoromethyl)-1,2,4-triazol-1-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (45 mg, 0.13 mmol, 1 eq) in EtOAc (0.5 mL) was added p- toluenesulfonic acid (29 mg, 0.17 mmol, 1.3 eq). The reaction mixture was stirred at 80 °C for 12 h and concentrated in vacuo. To the residue was added water and lyophilized to afford 4- methylbenzenesulfonic acid;6-[[5-(trifluoromethyl)-1,2,4-triazol-1-yl]methyl]-2- azaspiro[3.3]heptane (47 mg, 86% yield) as off-white solid. MS (ESI): m/z = 247.2 [M+H] ⁺ . In analogy to Building Block P.51, the following building blocks were generated using the relevant commercial building block for the SN2 reaction in Step 1. In some cases, the alternative salt trifluoroacetate was also used. Building Block P.54: 6-[[4-(Trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]h eptane; 4-methylbenzenesulfonic acid Step 1: tert-Butyl 6-[[4-(trifluoromethyl)pyrazol-1-yl]methylene]-2-azaspiro[3. 3]heptane-2- carboxylate To a solution of 4-(trifluoromethyl)-1H-pyrazole (2.43 g, 18 mmol, 3 eq), tert-butyl 6-[(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]-2-azaspiro[3. 3]heptane-2-carboxylate (2 g, 6 mmol, 1 eq, CAS 2763647-64-7) and pyridine (1.45 mL, 18 mmol, 3 eq) in DMSO (80 mL) was added copper diacetate (2.38 g, 12 mmol, 2 eq) under O2 atmosphere, then stirred at 100 °C for 12 h under O ₂ (balloon) condition. The aqueous phase was extracted with EtOAc (200 mL x 3). The combined organic phase was washed with brine (200 mL x 3), dried with anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by reversed-phase HPLC (0.1% FA condition) to afford tert-butyl 6-[[4-(trifluoromethyl)pyrazol-1-yl]methylene]-2- azaspiro[3.3]heptane-2-carboxylate (640 mg, 31% yield) as a brown solid. MS (ESI): m/z = 288.1 [M-C4H8+H] ⁺ . Step 2: tert-Butyl 6-[[4-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]h eptane-2- carboxylate To a solution of tert-butyl 6-[[4-(trifluoromethyl)pyrazol-1-yl]methylene]-2- azaspiro[3.3]heptane-2-carboxylate (690 mg, 2 mmol) in EtOAc (7 mL) was added wet Pd/C 10% (230 mg, 0.2 mmol). The reaction mixture was stirred at 25 °C under H ₂ atmosphere (balloon) for 2 h. The mixture was filtered and concentrated in vacuo to afford tert-butyl 6-[[4- (trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane -2-carboxylate (690 mg, 99% yield) as yellow solid. MS (ESI): m/z = 346.1 [M+H] ⁺ . Step 3: 6-[[4-(Trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]h eptane; 4- methylbenzenesulfonic acid A solution of tert-butyl 6-[[4-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]h eptane-2- carboxylate (675 mg, 1.95 mmol) and p-toluenesulfonic acid (404 mg, 2.35 mmol) in EtOAc (6 mL) was stirred at 80 °C for 12 h. The reaction mixture was concentrated in vacuo. To the residue was added deionized water and the mixture was lyophilized to afford 6-[[4- (trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane ; 4-methylbenzenesulfonic acid (794 mg, 96% yield) as white solid. MS (ESI): m/z = 246.2 [M+H] ⁺ . In analogy to Building Block P.54, the following building blocks were generated using the relevant heteroaryl compound for the Chan Lam-type coupling in Step 1. Building Blocks P.58 & P.59: 6-[[3-(Difluoromethyl)-5-methyl-pyrazol-1-yl]methyl]-2-azasp iro[3.3]heptane;4- methylbenzenesulfonic acid (P.58) 6-[[5-(Difluoromethyl)-3-methyl-pyrazol-1-yl]methyl]-2-azasp iro[3.3]heptane;4- methylbenzenesulfonic acid (P.59) Step 1: tert-Butyl 6-[[3-(difluoromethyl)-5-methyl-pyrazol-1-yl]methyl]-2-azasp iro[3.3]heptane- 2-carboxylate and tert-butyl 6-[[5-(difluoromethyl)-3-methyl-pyrazol-1-yl]methyl]-2-azasp iro[3.3]heptane-2- carboxylate To a solution of tert-butyl 6-(hydroxymethyl)-2-azaspiro[3.3]heptane-2-carboxylate (6 g, 26.4 mmol, 1 eq, CAS 1363381-93-4) in toluene (100 mL) was added 5-(difluoromethyl)-3-methyl- 1H-pyrazole (4.18 g, 31.7 mmol, 1.2 eq, CAS 934759-09-8) and 2- (tributylphosphoranylidene)acetonitrile (9.56 g, 39.6 mmol, 1.5 eq, CAS 157141-27-0). The mixture was stirred at 100 °C for 12 h. The reaction mixture was filtered and concentrated in vacuo. The residue was purified by prep-HPLC(Neutral condition,Welch Ultimate XB-CN 250*50*10um,Hexane-EtOH) and concentrated in vacuo to afford tert-butyl 6-[[3-(difluoromethyl)-5-methyl-pyrazol-1-yl]methyl]-2-azasp iro[3.3]heptane-2- carboxylate (2.7 g, 7.91 mmol, 30% yield) as light yellow powder. MS (ESI): m/z = 286.0 [M- C4H8+H] ⁺ and tert-butyl 6-[[5-(difluoromethyl)-3-methyl-pyrazol-1-yl]methyl]-2-azasp iro[3.3]heptane-2- carboxylate (3.6 g, 10.54 mmol, 40% yield) as light yellow oil. MS (ESI): m/z = 286.0 [M- C4H8+H] ⁺ . Step 2: 6-[[3-(Difluoromethyl)-5-methyl-pyrazol-1-yl]methyl]-2-azasp iro[3.3]heptane;4- methylbenzenesulfonic acid (P.58) To a solution of tert-butyl 6-[[3-(difluoromethyl)-5-methyl-pyrazol-1-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (2.85 g, 8.35 mmol, 1 eq) in EtOAc (15 mL) was added p- toluenesulfonic acid (1.72 g, 10 mmol, 1.2 eq). The mixture was stirred at 80 °C for 2 h. The reaction mixture was concentrated in vacuo to afford 6-[[3-(difluoromethyl)-5-methyl-pyrazol-1- yl]methyl]-2-azaspiro[3.3]heptane;4-methylbenzenesulfonic acid (3.45 g, 98% yield) as light yellow solid. MS (ESI): m/z = 242.1 [M+H] ⁺ . Step 2: 6-[[5-(Difluoromethyl)-3-methyl-pyrazol-1-yl]methyl]-2-azasp iro[3.3]heptane;4- methylbenzenesulfonic acid (P.59) To a solution of tert-butyl 6-[[5-(difluoromethyl)-3-methyl-pyrazol-1-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (3.88 g, 11.3 mmol, 1 eq) in ethyl acetate (20 mL) was added p-toluenesulfonic acid (2.32 g, 13.5 mmol, 1.2 eq). The mixture was stirred at 80 °C for 2 h. The reaction mixture was concentrated in vacuo to afford 6-[[5-(difluoromethyl)-3-methyl- pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane;4-methylbenzenes ulfonic acid (4.31 g, 90% yield) as light yellow oil. MS (ESI): m/z = 242.1 [M+H] ⁺ . Building Block P.62: 6-[[3-(Difluoromethyl)-1H-pyrazol-5-yl]methyl]-2- azaspiro[3.3]heptane;2,2,2-trifluoroacetic acid Step 1: tert-Butyl 6-[[5-(difluoromethyl)-2-(2-trimethylsilylethoxymethyl)pyraz ol-3- yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate To a mixture of 2-[[5-bromo-3-(difluoromethyl)pyrazol-1-yl]methoxy]ethyl-tri methyl-silane (5.3 g, 16.2 mmol, 1 eq, CAS 2416163-95-4), tert-butyl 6-[(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)methylene]-2-azaspiro[3.3]heptane-2-carbox ylate (5.97 g, 17.8 mmol, 1.1 eq, CAS 2763647-64-7) and potassium carbonate (4.47 g, 32.4 mmol, 2 eq) in 1,4-dioxane (50 mL) and water (5 mL) was added cyclopenta-2,4-dien-1- yl(diphenyl)phosphane;dichloromethane;dichloropalladium;iron (2+) (1.32 g, 1.62 mmol, 0.1 eq, CAS 95464-05-4) under N2. The mixture was stirred at 100 °C for 2 h under N2 atmosphere. The reaction mixture was poured into water (500 mL). The aqueous phase was extracted with EtOAc. The organic phase was washed with brine (600 mL), dried with anhydrous Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, petroleum ether/ethyl acetate=100/1 to 1/1) to afford tert-butyl 6-[[5-(difluoromethyl)-2-(2- trimethylsilylethoxymethyl)pyrazol-3-yl]methylene]-2-azaspir o[3.3]heptane-2-carboxylate (6.1 g, 13.39 mmol, 79% yield) as light yellow solid. MS (ESI): m/z = 456.3 [M+H] ⁺ . Step 2: tert-Butyl 6-[[5-(difluoromethyl)-2-(2-trimethylsilylethoxymethyl)pyraz ol-3-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[[5-(difluoromethyl)-2-(2-trimethylsilylethoxymethyl)pyraz ol-3- yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate (7 g, 15.36 mmol, 1 eq) in EtOAc (100 mL) was added Pd/C 10% (2 g, 4.61 mmol, 0.3 eq) under N ₂ atmosphere. The mixture was stirred at 25 °C for 0.5 h under H2 (15 PSI) atmosphere. The reaction mixture was filtered and concentrated in vacuo to afford tert-butyl 6-[[5-(difluoromethyl)-2-(2- trimethylsilylethoxymethyl)pyrazol-3-yl]methyl]-2-azaspiro[3 .3]heptane-2-carboxylate (6 g, 85% yield) as colorless oil. Step 3: 6-[[3-(Difluoromethyl)-1H-pyrazol-5-yl]methyl]-2-azaspiro[3. 3]heptane;2,2,2- trifluoroacetic acid To a solution of tert-butyl 6-[[5-(difluoromethyl)-2-(2-trimethylsilylethoxymethyl)pyraz ol-3- yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (6 g, 13.1 mmol, 1 eq) in dichloromethane (40 mL) was added 2,2,2-trifluoroacetic acid (20 mL) at 0 °C. The mixture was stirred at 20 °C for 16 h. The reaction mixture was concentrated in vacuo. The residue was purified by prep-HPLC (column: Phenomenex luna C18250*80mm*10 um;mobile phase: [water(TFA)-ACN];B%: 1%- 30%,20min) to afford 6-[[3-(difluoromethyl)-1H-pyrazol-5-yl]methyl]-2- azaspiro[3.3]heptane;2,2,2-trifluoroacetic acid (3.94 g, 87% yield) as white solid. MS (ESI): m/z = 228.2 [M+H] ⁺ . In analogy to Building Block P.62, the following building block was generated using the relevant heteroarylbromide for the reaction in Step 1. Building Block P.69: [4-(2-Azaspiro[3.3]heptan-6-ylmethyl)-3-fluoro-phenyl]-imino -oxo- (trifluoromethyl)-λ⁶-sulfane;4-methylbenzenesulfonic acid Step 1: 1-Bromo-2-methylsulfinyl-4-(trifluoromethyl)benzene 1-Bromo-2-methylsulfanyl-4-(trifluoromethyl)benzene (3.7 g, 13.6 mmol, 1 eq, CAS 142994- 07-8) was dissolved in trifluoroacetic acid (37 mL, 480 mmol, 35 eq). Hydrogen peroxide (1.15 mL, 13.6 mmol, 1 eq) in water (1.2 mL) was added at 0 °C. The mixture was stirred at RT for 12 h. The reaction mixture was concentrated in vacuo and diluted between DCM and NaHCO ₃ aq. solution. The organic layer was dried over Na2SO4 and concentrated in vacuo to afford 1-bromo- 2-methylsulfinyl-4-(trifluoromethyl)benzene (3.3 g, 11.49 mmol, 75% yield) as ligh yellow oil. MS (ESI): m/z = 288.9 [M+H] ⁺ . Step 2: [2-Bromo-5-(trifluoromethyl)phenyl]-imino-methyl-oxo-λ⁶-s ulfane A 30 mL sealed tube was charged with 1-bromo-2-methylsulfinyl-4-(trifluoromethyl)benzene (2.5 g, 8.7 mmol, 1 eq), amino 4-nitrobenzoate;trifluoromethanesulfonic acid (7.23 g, 21.7 mmol, 2.5 eq, CAS 2055895-59-3), ferrous sulfate (264 mg, 1.74 mmol, 0.2 eq, CAS 7720-78-7) and 1,10-phenanthroline (627 mg, 3.48 mmol, 0.4 eq, CAS 66-71-7) in ACN (20 mL). The reaction mixture was stirred at 30 °C for 48 h. After cooling to room temperature, the reaction mixture was quenched with a saturated NaHCO ₃ solution (5 mL). The organic layer was separated, dried over anhydrous Na ₂ SO ₄ and concentrated in vacuo. The crude product was purified by flash chromatography (silica gel, 120g, 0% to 50% acetonitrile in chloroform) to afford [2-bromo-5-(trifluoromethyl)phenyl]-imino-methyl-oxo-λ6-sul fane (900 mg, 3 mmol, 30% yield) as light yellow solid. MS (ESI): m/z = 302/304 [M+H] ⁺ . Step 3: tert-Butyl 6-[[2-(methylsulfonimidoyl)-4-(trifluoromethyl)phenyl]methyl ene]-2- azaspiro[3.3]heptane-2-carboxylate To a stirred suspension of tert-butyl 6-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]- 2-azaspiro[3.3]heptane-2-carboxylate (998 mg, 3 mmol, 1 eq, CAS 2763647-64-7), [2-bromo-5- (trifluoromethyl)phenyl]-imino-methyl-oxo-λ6-sulfane (900 mg, 3 mmol, 1 eq) and potassium carbonate (823 mg, 6 mmol, 2 eq) in 1,4-dioxane (30 mL) and water (6 mL), 1,1'- bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (364 mg, 0.45 mmol, 0.15 eq, CAS 95408-45-0) was added. The reaction mixture was stirred at 110° C for 48 h. The reaction mixture was concentrated in vacuo and diluted between EtOAc and brine. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude product was purified by flash chromatography (silica gel, 80g, hexane/tert-butylmethylether/methanol) to afford tert- butyl 6-[[2-(methylsulfonimidoyl)-4-(trifluoromethyl)phenyl]methyl ene]-2- azaspiro[3.3]heptane-2-carboxylate (450 mg, 32% yield) as white solid. MS (ESI): m/z = 375.2 [M-C4H8+H] ⁺ . Step 4: tert-Butyl 6-[[2-(methylsulfonimidoyl)-4-(trifluoromethyl)phenyl]methyl ]-2- azaspiro[3.3]heptane-2-carboxylate tert-Butyl 6-[[2-(methylsulfonimidoyl)-4-(trifluoromethyl)phenyl]methyl ene]-2- azaspiro[3.3]heptane-2-carboxylate (320 mg, 0.74 mmol, 1 eq) was dissolved in EtOAc (30 mL) and hydrogenated at 22800 mmHg over palladium/C (79 mg, 0.07 mmol, 0.1 eq) for 10 h. The reaction mixture was filtered and concentrated in vacuo to afford tert-butyl 6-[[2- (methylsulfonimidoyl)-4-(trifluoromethyl)phenyl]methyl]-2-az aspiro[3.3]heptane-2-carboxylate (300 mg, 86% yield) as colorless oil. MS (ESI): m/z = 333.2 [M-C4H8+H] ⁺ . Step 5: [4-(2-Azaspiro[3.3]heptan-6-ylmethyl)-3-fluoro-phenyl]-imino -oxo-(trifluoromethyl)-λ⁶- sulfane;4-methylbenzenesulfonic acid p-Toluenesulfonic acid monohydrate (158 mg, 0.83 mmol, 1.2 eq) was added to a stirred solution of tert-butyl 6-[[2-(methylsulfonimidoyl)-4-(trifluoromethyl)phenyl]methyl ]-2- azaspiro[3.3]heptane-2-carboxylate (300 mg, 0.69 mmol, 1 eq) in EtOAc (30 mL). The reaction mixture was stirred at RT for 16 h. The reaction mixture was concentrated in vacuo. The residue was purified by HPLC to afford [2-(2-azaspiro[3.3]heptan-6-ylmethyl)-5- (trifluoromethyl)phenyl]-imino-methyl-oxo-λ6-sulfane;4-meth ylbenzenesulfonic acid (137 mg, 37% yield) as white solid. MS (ESI): m/z = 333.0 [M+H] ⁺ . In analogy to Building Block P.69, the following building blocks were generated using the relevant bromo-methylsulfanylbenzene compound for the reaction in Step 1. Building Block P.113: 2,2,2-trifluoroacetic acid;6-[[5-[1- (trifluoromethyl)cyclopropyl]pyrimidin-2-yl]methyl]-2-azaspi ro[3.3]heptane To a solution of 6-[[5-[1-(trifluoromethyl)cyclopropyl]pyrimidin-2-yl]methyl] -2- azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (180 mg, 452 µmol, 1 eq) in dichloromethane (1.5 mL) was added TFA (516 mg, 348 uL, 4.53 mmol, 10 eq). The reaction mixture was stirred at RT for 18 h. The reaction mixture was concentrated in vacuo to give 365 mg of the crude desired product as a brownish viscous oil, purity ~50%. MS (ESI): m/z = 298.2 [M+H] ⁺ . Step 1: tert-butyl 6-[(5-bromopyrimidin-2-yl)methylene]-2-azaspiro[3.3]heptane- 2-carboxylate To a solution of tert-butyl 6-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]-2 - azaspiro[3.3]heptane-2-carboxylate (5.88 g, 17.55 mmol, 1 eq, CAS 2763647-64-7), 5-bromo-2- iodopyrimidine (5 g, 17.55 mmol, 1 eq) in 1,4-dioxane (75 mL) and water (15 mL), was added potassium carbonate (4.85 g, 35.1 mmol, 2 eq) and 1,1'-bis(diphenylphosphino)ferrocene- palladium(II)dichloride dichloromethane complex (1.43 g, 1.76 mmol, 0.1 eq, CAS 95464-05-4 ) at 20°C. The mixture was stirred at 80 °C under N2 atmosphere for 12 h. The residue was purified by flash chromatography on silica gel eluting with PE/EtOAc (5:1) to afford tert-butyl 6-[(5-bromopyrimidin-2-yl)methylene]-2-azaspiro[3.3]heptane- 2-carboxylate (4.6 g, 12.56 mmol, 71% yield) as white solid. MS (ESI): m/z = 312.0 [M-C4H8+H] ⁺ . Step 2: tert-butyl 6-[(5-bromopyrimidin-2-yl)methyl]-2-azaspiro[3.3]heptane-2-c arboxylate To a solution of tert-butyl 6-[(5-bromopyrimidin-2-yl)methylene]-2-azaspiro[3.3]heptane- 2- carboxylate (4.8 g, 13.11 mmol, 1 eq) in EtOAc (48 mL) was added PtO2 (1.63 g, 7.19 mmol, 0.55 eq) at 25 °C under N2. The mixture was stirred at 25 °C under H2 atmosphere (15 PSI) for 2.5 h. The reaction mixture was filtered and the residue was purified by flash chromatography on silica gel eluting with PE/EtOAc (3:1) to afford tert-butyl 6-[(5-bromopyrimidin-2-yl)methyl]-2- azaspiro[3.3]heptane-2-carboxylate (1.87 g, 5.08 mmol, 38% yield) as white solid. MS (ESI): m/z = 314.0 [M-C ₄ H ₈ +H] ⁺ . Step 3: tert-butyl 6-[[5-[1-(trifluoromethyl)vinyl]pyrimidin-2-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate To a solution of 4,4,6-trimethyl-2-[1-(trifluoromethyl)vinyl]-1,3,2-dioxabori nane (1.52 g, 6.84 mmol, 1.2 eq, CAS 1011460-68-6) and tert-butyl 6-[(5-bromopyrimidin-2-yl)methyl]-2- azaspiro[3.3]heptane-2-carboxylate (2.1 g, 5.7 mmol, 1 eq), potassium carbonate (1.58 g, 11.4 mmol, 2 eq) in 1,4-dioxane (20 mL) and water (4 mL) was added 1,1'- bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (465 mg, 0.57 mmol, 0.1 eq, CAS 95464-05-4). The mixture was stirred at 80 °C under N2 atmosphere for 12 h. The reaction mixture was poured into water (50 mL) and extracted with ethyl acetate (15mL x 3). The organic layer was washed with brine and dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with PE/EtOAc (3:1) to afford tert-butyl 6-[[5-[1-(trifluoromethyl)vinyl]pyrimidin-2- yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (2.05 g, 5.35 mmol, 93% yield) as white solid. MS (ESI): m/z = 328.0 [M-C4H8+H] ⁺ . Step 4: tert-butyl 6-[[5-[1-(trifluoromethyl)cyclopropyl]pyrimidin-2-yl]methyl] -2- azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[[5-[1-(trifluoromethyl)vinyl]pyrimidin-2-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (2.05 g, 5.35 mmol, 1 eq) in THF (35 mL) was added diphenyl(methyl)sulfonium tetrafluoroborate (2 g, 6.95 mmol, 1.3 eq, CAS 10504-60-6). NaHMDS/THF (8.55 mL, 8.55 mmol, 1.6 eq) was added dropwise at 0 °C. The reaction mixture was stirred at 25 °C for 1 h. The reaction mixture was poured into saturated NH4Cl aqueous solution (80 mL) and extracted with ethyl acetate (20 mL x 3). The organic layer was washed with brine and dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with PE/EtOAc (2:1) to afford the crude. The crude product was purified by prep-HPLC (Column, [Phenomenex luna C18250*50mm*10 um]; mobile phase: [ACN] and [H2O] (conditions: [water(0.225%FA)-ACN], B%: 65%-90%; Detector, UV 254 nm. RT: [22 min]) to afford tert-butyl 6-[[5-[1- (trifluoromethyl)cyclopropyl]pyrimidin-2-yl]methyl]-2-azaspi ro[3.3]heptane-2-carboxylate (1.1 g, 2.78 mmol, 52% yield) as white solid. MS (ESI): m/z = 342.1 [M-C ₄ H ₈ +H] ⁺ . In analogy to Building Block P.113, the following building blocks were generated using the relevant heteroarylbromide or heteroarylchloride. Building Block P.119: 6-[[4-(trifluoromethylsulfonyl)pyrazol-1-yl]methyl]-2- azaspiro[3.3]heptane 4-methylbenzenesulfonic acid A mixture of tert-butyl 6-[[4-(trifluoromethylsulfonyl)pyrazol-1-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (630 mg, 1.54 mmol) and p-toluenesulfonic acid (317 mg, 1.85 mmol, 1.2 eq) in EtOAc (20 mL) was stirred at 80 °C for 12 h under N2 balloon. The reaction mixture was concentrated in vacuo and the residue was dissolved in H ₂ O (30 mL). The solution was lyophilized to afford 6-[[4-(trifluoromethylsulfonyl)pyrazol-1-yl]methyl]-2- azaspiro[3.3]heptane 4-methylbenzenesulfonic acid (738 mg, 1.53 mmol, 97 % yield) as a light yellow solid. MS (ESI): m/z = 310.1 [M+H] ⁺ . Step 1: tert-butyl 6-[(4-iodopyrazol-1-yl)methylene]-2-azaspiro[3.3]heptane-2-c arboxylate To a solution of tert-butyl 6-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]-2 - azaspiro[3.3]heptane-2-carboxylate (45.6 g, 136 mmol, CAS 2763647-64-7), 4-iodopyrazole (24.0 g, 123 mmol), boric acid (7.65 g, 123 mmol) and pyridine (30 mL, 371 mmol) in DCE (230 mL) was added copper diacetate (49.4 g, 247 mmol) under O2 atmosphere. The mixture was stirred at 70 °C for 12 h under O2 atmosphere. The reaction mixture was concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with PE/EtOAc (4:1) to afford the crude product, which was purified by prep-HPLC (water(FA)-ACN 55%- 75%) to afford the title compound (17.7 g, 44.1 mmol, 35.6 % yield) as a white solid. MS (ESI): m/z = 346.0 [M-C ₄ H ₈ +H] ⁺ . Step 2: tert-butyl 6-[[4-(trifluoromethylsulfanyl)pyrazol-1-yl]methylene]-2- azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[(4-iodopyrazol-1-yl)methylene]-2-azaspiro[3.3]heptane-2- carboxylate (30 mg, 0.07 mmol) in ACN (3 mL) was added silver(I) trifluoromethanethiolate (46.9 mg, 0.22 mmol, CAS 811-68-7) , CuI (28.5 mg, 0.15 mmol) and 2-pyridin-2-ylpyridine (23.4 mg, 0.15 mmol) in a sealed tube. The reaction mixture was stirred at 90 °C for 12 h. The reaction mixture was concentrated in vacuo.The residue was purified by prep-HPLC (water (FA)-ACN] 52%-82%); to afford the title compound (13.0 mg, 0.03 mmol, 46 % yield) as a yellow solid. MS (ESI): m/z = 320.1 [M-C4H8+H] ⁺ . Step 3: tert-butyl 6-[[4-(trifluoromethylsulfanyl)pyrazol-1-yl]methyl]-2-azaspi ro[3.3]heptane-2- carboxylate To a solution of tert-butyl 6-[[4-(trifluoromethylsulfanyl)pyrazol-1-yl]methylene]-2- azaspiro[3.3]heptane-2-carboxylate (2.8 g, 7.46 mmol) in EtOAc (50 mL) was added Pd/C (1 g, 0.75 mmol) at 25 °C and stirred for 1 h under H ₂ balloon (760 mm Hg). The reaction mixture was filtered and concentrated in vacuo to afford the title compound (2.8 g, 7.42 mmol, 99 % yield) as a white solid. MS (ESI): m/z = 322.2 [M-C4H8+H] ⁺ . Step 4: tert-butyl 6-[[4-(trifluoromethylsulfonyl)pyrazol-1-yl]methyl]-2-azaspi ro[3.3]heptane-2- carboxylate To a solution of tert-butyl 6-[[4-(trifluoromethylsulfanyl)pyrazol-1-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (1 g, 2.65 mmol) in 1,2-dichloroethane (4 mL), ACN (4 mL) and water (8 mL) was added sodium periodate (1.13 g, 5.3 mmol, CAS 811-68-7) and ruthenium(III) chloride hydrate (59.7 mg, 0.26 mmol, CAS 14898-67-0) at 0 °C, then the mixture was stirred at 25 °C for 12 h. The reaction was concentrated in vacuo. The residue was purified by prep-HPLC (water(FA)-ACN 50%-80%) to afford the title compound (630 mg, 1.54 mmol, 58 % yield) as a grey solid. MS (ESI): m/z = 354.3 [M-C4H8+H] ⁺ . Building Block P.123: 6-[[1-cyclopropyl-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2- azaspiro[3.3]heptane; 4-methylbenzenesulfonic acid To the mixture of tert-butyl 6-[[1-cyclopropyl-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (790 mg, 2.05 mmol) in EtOAc (8 mL) was added p- toluenesulfonic acid (388 mg, 2.25 mmol) at 25 °C. The reaction mixture was stirred at 80 °C for 12 h and concentrated in vacuo.20 mL deionized water and 2 mL ACN was added to the residue, which was lyophilized to give the title compound (811 mg, 1.77 mmol, 85% yield) as a yellow oil. MS (ESI): m/z = 286.1 [M-TsOH+H] ⁺ . Step 1: tert-butyl 6-[[5-(trifluoromethyl)-1H-pyrazol-4-yl]methylene]-2-azaspir o[3.3]heptane-2- carboxylate To the solution of tert-butyl 6-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]-2 - azaspiro[3.3]heptane-2-carboxylate (5 g, 14.9 mmol, CAS 2763647-64-7), 4-bromo-5- (trifluoromethyl)-1H-pyrazole (2.92 g, 13.6 mmol) in 1,4-dioxane (73 mL), water (14.6 mL) was added potassium carbonate (3.75 g, 27.2 mmol) and 1,1'-bis(diphenylphosphino)ferrocene- palladium(II)dichloride dichloromethane complex (554 mg, 0.68 mmol) at 20 °C. The the reaction mixture was stirred at 100 °C for 12 h under N2. The reaction mixture was filtered and concentrated in vacuo to give a residue which was purified by flash silica gel chromatography (eluent of 0-40% ethyl acetate/petroleum ether) to give a crude product which was further purified by flash silica gel chromatography (eluent of 0-40% ethyl acetate/petroleum ether) to give the title compound (790 mg, 2.3 mmol, 17 % yield) as a yellow oil. MS (ESI): m/z = 288.0 [M-C ₄ H ₈ +H] ⁺ . Step 2: tert-butyl 6-[[1-cyclopropyl-3-(trifluoromethyl)pyrazol-4-yl]methylene] -2- azaspiro[3.3]heptane-2-carboxylate To a mixture of tert-butyl 6-[[5-(trifluoromethyl)-1H-pyrazol-4-yl]methylene]-2- azaspiro[3.3]heptane-2-carboxylate (600 mg, 1.75 mmol), cyclopropylboronic acid (600 mg, 6.99 mmol) in DCE (6 mL) was added pyridine (0.42 mL, 5.24 mmol), boric acid (108 mg, 1.75 mmol), copper diacetate (698 mg, 3.5 mmol) at 20 °C. The reaction mixture was stirred at 100 °C for 16 h under O ₂ (balloon). The reaction mixture was filtered and diluted with water 50 mL and extracted with EtOAc 150 mL (50 mL x 3). The combined organic layers were washed with brine (40 mL), dried over Na ₂ SO ₄ , filtered and concentrated in vacuo to give a residue which was purified by silica gel chromatography (0-28% ethyl acetate/petroleum ether) to give the title compound (350 mg, 0.91 mmol, 52 %) as a colorless oil. MS (ESI): m/z = 328.0 [M-C4H8+H] ⁺ . Step 3: tert-butyl 6-[[1-cyclopropyl-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate To the mixture of tert-butyl 6-[[1-cyclopropyl-3-(trifluoromethyl)pyrazol-4-yl]methylene] -2- azaspiro[3.3]heptane-2-carboxylate (720 mg, 1.88 mmol) in EtOAc (15 mL) was added Pd/C (wet, 216 mg, 10 %) at 25 °C. The reaction mixture was stirred at 25 °C for 0.5 h under H ₂ (15 Psi). The reaction mixture was filtered and the filter liquor was concentrated in vacuo to give the title compound (640 mg, 1.66 mmol, 88% yield) as a colorless oil. MS (ESI): m/z = 330.0 [M- C ₄ H ₈ +H] ⁺ . Building Block P.126: [1-(2-azaspiro[3.3]heptan-6-ylmethyl)pyrazol-4-yl]-imino-oxo - (trifluoromethyl)-λ⁶-sulfane; 4-methylbenzenesulfonic acid A mixture of tert-butyl 6-[[4-(trifluoromethylsulfonimidoyl)pyrazol-1-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (650 mg, 1.59 mmol) and p-toluenesulfonic acid (329 mg, 1.91 mmol) in EtOAc (10 mL) was stirred at 80 °C for 12 h under N2 balloon. The reaction mixture was concentrated in vacuo and the residue was dissolved in H ₂ O (30 mL). The solution was lyophilized to give the title compound (623 mg, 1.3 mmol, 77 % yield) as light yellow oil. MS (ESI): m/z = 309.1 [M+H] ⁺ . Step 1: tert-butyl 6-[[4-(trifluoromethylsulfonimidoyl)pyrazol-1-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate A mixture of tert-butyl 6-[[4-(trifluoromethylsulfanyl)pyrazol-1-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (P.119, Step 3) (1.8 g, 4.77 mmol), PhI(OAc)2 (6.14 g, 19.1 mmol) and ammonium carbamate (1.49 g, 19.1 mmol) in trifluoroethanol was stirred at 30 °C for 12 h. The mixture was concentrated in vacuo. The residue was purified by prep-HPLC (water (FA)-ACN, 60%-80%) to afford the title compound (650 mg, 1.59 mmol, 33 % yield) as a grey solid. MS (ESI): m/z = 353.1 [M-C ₄ H ₈ +H] ⁺ . Building Blocks P.132 and P.156: 4-methylbenzenesulfonic acid;6-[[2-(2,2,2-trifluoroethyl)- 5-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]hepta ne and 4- methylbenzenesulfonic acid;6-[[1-(2,2,2-trifluoroethyl)-5-(trifluoromethyl)pyrazol -3- yl]methyl]-2-azaspiro[3.3]heptane A solution of p-toluenesulfonic acid (247 mg, 1.43 mmol) and tert-butyl 6-[[2-(2,2,2- trifluoroethyl)-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2-az aspiro[3.3]heptane-2-carboxylate (510 mg, 1.19 mmol) in EtOAc (5 mL) was stirred at 80 °C for 12 h. The mixture was concentrated in vacuo. To the residue was added deionized water and lyophilized to give the title compound (550 mg, 1.1 mmol, 92% yield) as a colorless oil. MS (ESI): m/z =328.0 [M+ H] ⁺ . Step 1:tert-butyl 6-[[5-(trifluoromethyl)-1H-pyrazol-3-yl]methylene]-2-azaspir o[3.3]heptane-2- carboxylate To a solution of 3-bromo-5-(trifluoromethyl)-1H-pyrazole (9 g, 41.87 mmol, 1 eq, CAS 93608- 11-8), tert-butyl 6-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]-2 - azaspiro[3.3]heptane-2-carboxylate (14 g, 41.8 mmol, 1 eq CAS 2763647-64-7), potassium carbonate (11.57 g, 83.7 mmol, 2 eq) in 1,4-dioxane (10 mL) and water (2 mL) was added 1,1'- bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (3.42 g, 4.19 mmol, 0.1 eq, CAS 95464-05-4) at 25 °C. The reaction mixture was stirred at 80 °C for 12 h under N ₂ . The reaction mixture was concentrated in vacuo. The residue was purified by flash silica gel chromatography (Silica Flash Column, Eluent of 0~46% Ethyl acetate/petroleum ethergradient)(petroleum:ethyl acetate=1:1, Rf=0.6) to give tert-butyl 6-[[5-(trifluoromethyl)- 1H-pyrazol-3-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxyl ate (7.0 g, 20.3 mmol, 48% yield) as white solid. MS (ESI): m/z =288.0 [M-C4H8+H] ⁺ . Step 2: tert-butyl 6-[[5-(trifluoromethyl)-1H-pyrazol-3-yl]methyl]-2-azaspiro[3 .3]heptane-2- carboxylate To a solution of tert-butyl 6-[[5-(trifluoromethyl)-1H-pyrazol-3-yl]methylene]-2- azaspiro[3.3]heptane-2-carboxylate (1.26 g, 3.67 mmol, 1 eq) in EtOAc (20 mL)was added wet Pd/C (505 mg, 0.65 mmol, 0.18 eq) under N2. The suspension was degassed under vacuum and purged with H ₂ . The reaction was stirred under H ₂ (15 psi) at 25 °C for 0.5 h. The reaction mixture was filtered and the filtrate was concentrated in vacuo to give tert-butyl 6-[[5- (trifluoromethyl)-1H-pyrazol-3-yl]methyl]-2-azaspiro[3.3]hep tane-2-carboxylate (1.26 g, 3.65 mmol, 99% yield) as colorless oil. MS (ESI): m/z =290.0 [M-C ₄ H ₈ +H] ⁺ . Step 3: tert-butyl 6-[[2-(2,2,2-trifluoroethyl)-5-(trifluoromethyl)pyrazol-3-yl ]methyl]-2- azaspiro[3.3]heptane-2-carboxylate and tert-butyl 6-[[1-(2,2,2-trifluoroethyl)-5- (trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptane -2-carboxylate To a solution of tert-butyl 6-[[5-(trifluoromethyl)-1H-pyrazol-3-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (13.7 g, 39.67 mmol, 1 eq) in THF (278 mL) was added NaH (2.38 g, 59.5 mmol, 1.5 eq) at 0 °C for 0.5 h.2,2,2-trifluoroethyl trifluoromethanesulfonate (18.41 g, 79.3 mmol, 2 eq, CAS 6226-25-1) was added at 20 °C. The reaction mixture was stirred for 12 h at room temperature. The reaction mixture was quenched slowly by ice and extracted with EtOAc. The organic phase was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by prep-HPLC (Welch Ultimate XB-SiOH 250*50*10um,Hexane-EtOH(0.1% NH3.H2O)) and concentrated in vacuo to give tert-butyl 6-[[1-(2,2,2-trifluoroethyl)-5-(trifluoromethyl)pyrazol-3-yl ]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (2 g, 4.68 mmol, 11% yield) as colorless oil. MS (ESI): m/z =372.1 [M-C ₄ H ₈ +H] ⁺ and tert-butyl 6-[[2-(2,2,2-trifluoroethyl)-5-(trifluoromethyl)pyrazol-3- yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (8.74 g, 20.45 mmol, 51% yield) as white solid. MS (ESI): m/z =372.1 [M-C4H8+H] ⁺ . Step 4: 4-methylbenzenesulfonic acid;6-[[2-(2,2,2-trifluoroethyl)-5-(trifluoromethyl)pyrazol -3- yl]methyl]-2-azaspiro[3.3]heptane (P.132) and 6-[[1-(2,2,2-trifluoroethyl)-5- (trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptane (P.156). In analogy to Building Block P.1, Step 3, tert-butyl 6-[[2-(2,2,2-trifluoroethyl)-5- (trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptane -2-carboxylate and tert-butyl 6-[[1- (2,2,2-trifluoroethyl)-5-(trifluoromethyl)pyrazol-3-yl]methy l]-2-azaspiro[3.3]heptane-2- carboxylate were treated with 4-methylbenzenesulfonic acid monohydrate in EtOAc at 80 °C for 12 h to give 4-methylbenzenesulfonic acid;6-[[2-(2,2,2-trifluoroethyl)-5- (trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptane (586 mg, 1.17 mmol, 98% yield) as cololess oil. MS (ESI): m/z = 328.0 [M+ H] ⁺ (P.132) and 4-methylbenzenesulfonic acid;6- [[1-(2,2,2-trifluoroethyl)-5-(trifluoromethyl)pyrazol-3-yl]m ethyl]-2-azaspiro[3.3]heptane (2.06 g, 4.13 mmol, 88% yield) as a off-white solid. MS (ESI): m/z = 328.0 [M+ H] ⁺ . (P.156). Building Block P.136: 4-methylbenzenesulfonic acid;6-[[1-(2,2,2-trifluoroethyl)-3- (trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptane To a mixture of tert-butyl 6-[[1-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl ]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (1.05 g, 2.46 mmol, 1 eq) in EtOAc (10 mL) was added p- toluenesulfonic acid (465 mg, 2.7 mmol, 1.1 eq) at 20 °C. The reaction mixture was stirred at 80 °C for 12 h. The reaction mixture was concentrated in vacuo.20 mL deionized water and 2 mL acetonitrile were added, then lyophilized to give 4-methylbenzenesulfonic acid;6-[[1-(2,2,2- trifluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-az aspiro[3.3]heptane (1.22 g, 2.45 mmol, 99% yield) as light yellow oil. MS (ESI): m/z = 328.0 [M+ H] ⁺ . Step1: tert-butyl 6-[[5-(trifluoromethyl)-1H-pyrazol-4-yl]methylene]-2-azaspir o[3.3]heptane-2- carboxylate A solution of 4-bromo-5-(trifluoromethyl)-1H-pyrazole (8.35 g, 38.84 mmol, 1 eq, CAS 19968- 17-3), tert-butyl 6-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]-2 - azaspiro[3.3]heptane-2-carboxylate (14.32 g, 42.73 mmol, 1.1 eq, CAS 2763647-64-7), Cs2CO3 (77.69 mL, 116.53 mmol, 3 eq) in 2-methylbutan-2-ol (90 mL, 821 mmol, 21 eq) was added Ad2nBuP-Pd-G3 (2.82 g, 3.88 mmol, 0.1 eq, CAS 1651823-59-4) under N ₂ atmosphere. The reaction mixture was stirred at 90 °C for 16 h. The reaction mixture was poured into water (500 mL), extracted with EtOAc (400 mL). The organic phase was washed with brine (800 mL), dried over Na ₂ SO ₄ and purified by column chromatography (SiO ₂ , PE/AcOEt=1/0 to 1/1, PE/AcOEt=1/1, the desired product Rf=0.3 ) to give tert-butyl 6-[[5-(trifluoromethyl)-1H- pyrazol-4-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate (9 g, 26.2 mmol, 67% yield) as yellow oil. MS (ESI): m/z = 288.1 [M-C4H8+H] ⁺ . To the mixture of tert-butyl 6-[[5-(trifluoromethyl)-1H-pyrazol-4-yl]methylene]-2- azaspiro[3.3]heptane-2-carboxylate (2 g, 5.83 mmol, 1 eq), cesium carbonate (5.69 g, 17.48 mmol, 3 eq) in DMF (20 mL) was added a solution of 2,2,2-trifluoroethyl trifluoromethanesulfonate (2.7 g, 11.65 mmol, 2 eq, CAS 6226-25-1) in DMF (2 mL) at 0 °C. The mixture was stirred at 20 °C for 12 h. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (100 mL x 3). The combined organic layers were washed with aq.sat.NaCl 50 mL (50 mL), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash silica gel chromatography (ISCO@; 80 g SepaFlash@ Silica Flash Column, Eluent of 0~28% EtOAc/PE gradient @ 60 mL/min, Rf=0.45) to give tert-butyl 6-[[1- (2,2,2-trifluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]methy lene]-2-azaspiro[3.3]heptane-2- carboxylate (1.1 g, 2.59 mmol, 44% yield) as a white solid. MS (ESI): m/z = 370.0 [M- C4H8+H] ⁺ . Step 3: tert-butyl 6-[[1-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl ]methyl]-2- azaspiro[3.3]heptane-2-carboxylate To the mixture of tert-butyl 6-[[1-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)pyrazol-4- yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate (1 g, 2.35 mmol, 1 eq) in EtOAc (10 mL) was added Pd/C (300 mg, 10 %, wet.) at 20 °C. The reaction mixture was stirred at 20 °C for 1 h under H ₂ . The reaction mixture was filtered and concentrated in vacuo to give tert-butyl 6-[[1- (2,2,2-trifluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]methy l]-2-azaspiro[3.3]heptane-2- carboxylate (1.05 g, 2.46 mmol, 104% yield) as a colorless oil. MS (ESI): m/z = 372.0 [M- C4H8+H] ⁺ . In analogy to Building Block P.136, the following building block was generated using the relevant heteroarylhalide for the cross coupling in Step 1. Building Block P.137: 2-[6-(2-azaspiro[3.3]heptan-6-ylmethyl)-3- (trifluoromethyl)pyrrolo[2,3-b]pyridin-1-yl]ethanol;4-methyl benzenesulfonic acid A solution of 6-[[1-[2-[tert-butyl(dimethyl)silyl]oxyethyl]-3-(trifluorome thyl)pyrrolo[2,3- b]pyridin-6-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (80 mg, 144.47 µmol, 1 eq) and p-toluenesulfonic acid monohydrate (56 mg, 296 µmol, 2.05 eq) in ethyl acetate (0.5 mL) was stirred at reflux for 20 minutes in a sealed vial. The suspension was allowed to cool to RT and then filtered. The filter cake was washed with ethyl acetate to afford 2-[6-(2- azaspiro[3.3]heptan-6-ylmethyl)-3-(trifluoromethyl)pyrrolo[2 ,3-b]pyridin-1-yl]ethanol;4- methylbenzenesulfonic acid as colorless solid (82 mg, 78% yield). MS (ESI): m/z = 340.2 [M+H] ⁺ . Step 1: tert-butyl 6-[[3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl]methyl ene]-2- azaspiro[3.3]heptane-2-carboxylate A mixture of 6-bromo-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine (565 mg, 2.13 mmol, 1.1 eq, CAS 1934574-07-8), 6-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]-2 - azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (650 mg, 1.94 mmol, 1 eq, CAS 2763647-64-7), chloro(crotyl)(tri-tert-butylphosphine)palladium(II) (38 mg, 96.94 µmol, 0.05 eq, CAS 1334497-00-5) and tripotassium phosphate (823 mg, 3.88 mmol, 2 eq) in 1,4-dioxane (13 mL) and water (1.3 mL) was degassed with argon. The solution was stirred at 70 °C in a sealed vial overnight. The reaction mixture was poured on water and ethyl acetate and the layers were separated. The aqueous layer was extracted with ethyl acetate. The organic layers were washed with brine, dried over MgSO ₄ , filtered and concentrated in vacuo. The product was purified by silica gel chromatography on a 25 g column using an MPLC (ISCO) system eluting with a gradient of n-heptane : ethyl acetate (100 : 0 to 0 : 100) to afford tert-butyl 6-[[3- (trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl]methylene]-2 -azaspiro[3.3]heptane-2- carboxylate as light yellow solid (0.323 g, 40% yield). MS (ESI): m/z = 394.2 [M+H] ⁺ . Step 2: tert-butyl 6-[[3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl]methyl ]-2- azaspiro[3.3]heptane-2-carboxylate To a solution oftert-butyl 6-[[3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl]methyl ene]-2- azaspiro[3.3]heptane-2-carboxylate (500 mg, 1.27 mmol, 1 eq)inEtOAc (8 mL) was added wet Pd/C (175 mg, 0.22 mmol, 0.18 eq) under N2. The suspension was degassed under vacuum and purged with H2. The reaction mixture was stirred under H2(15 psi) at 25 °C for 0.5 h. The reaction mixture was filtered and the filtrate was concentrated in vacuo to give tert-butyl 6-[[3- (trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl]methyl]-2-az aspiro[3.3]heptane-2-carboxylate (440 mg, 1.11 mmol, 85% yield) as light brown solid. MS (ESI): m/z = 340.0 [M-C4H8+H] ⁺ . Step 3: 6-[[1-[2-[tert-butyl(dimethyl)silyl]oxyethyl]-3-(trifluorome thyl)pyrrolo[2,3-b]pyridin-6- yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester To an ice-cold solution of 6-[[3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl]methyl ]-2- azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (186 mg, 470 µmol, 1 eq) in DMF (1.5 mL) was added NaH (20 mg, 517.42 µmol, 1.1 eq) and the mixture was stirred for 30 minutes at this temperature. After addition of (2-bromoethoxy)-tert-butyldimethylsilane (123 mg, 111.52 uL, 517.42 µmol, 1 eq) stirring was continued at RT overnight. The mixture was poured on half- saturated aqueous NH ₄ Cl solution and ethyl acetate and the layers were separated. The aqueous layer was extracted twice with ethyl acetate. The organic layers were washed twice with water, dried over MgSO4, filtered, and concentrated in vacuo. The product was purified by silica gel chromatography on a 4 g column using an MPLC (ISCO) system eluting with a gradient of n- heptane : ethyl acetate (100 : 0 to 65 : 35) to afford 6-[[1-[2-[tert-butyl(dimethyl)silyl]oxyethyl]- 3-(trifluoromethyl)pyrrolo[2,3-b]pyridin-6-yl]methyl]-2-azas piro[3.3]heptane-2-carboxylic acid tert-butyl ester as colorless oil (208 mg, 79% yield). MS (ESI): m/z = 554.4 [M+H] ⁺ . Building Block P.143: 6-[difluoro-[6-(trifluoromethyl)-3-pyridyl]methyl]-2- azaspiro[3.3]heptane; 4-methylbenzenesulfonic acid To a solution of 6-[difluoro-[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspir o[3.3]heptane-2- carboxylic acid tert-butyl ester (77 mg, 196 µmol ) in isopropyl acetate (3 mL) was added p- toluenesulfonic acid monohydrate (82 mg, 432 µmol). The mixture was stirred at 80 °C for 3 h. The reaction mixture was concentrated in vacuo to afford 6-[difluoro-[6-(trifluoromethyl)-3- pyridyl]methyl]-2-azaspiro[3.3]heptane; 4-methylbenzenesulfonic acid (163 mg, 99 yield %) as colorless oil. MS (ESI): m/z = 293.0 [M+H] ⁺ . Step 1: tert-butyl 6-[6-(trifluoromethyl)pyridine-3-carbonyl]-2-azaspiro[3.3]he ptane-2- carboxylate To a solution of tert-butyl 6-[methoxy(methyl)carbamoyl]-2-azaspiro[3.3]heptane-2-carbox ylate (4.3 g, 15.1 mmol, CAS 2428601-18-5) and 5-bromo-2-(trifluoromethyl)pyridine (6.83 g, 30.2 mmol, CAS 436799-32-5) in THF (100 mL) was added n-BuLi (18.2 mL, 45.4 mmol) at -78 °C for 1 h. The reaction mixture was stirred at 30 °C for 12 h. The reaction mixture was poured into saturated NH4Cl aqueous solution (500 mL) and extracted with ethyl acetate. The organic layer was washed with brine. The residue was purified by flash chromatography on silica gel eluting with PE/EtOAc (2:1) to afford the title compound (1400 mg, 3.78 mmol, 25 % yield) as a brown solid. MS (ESI): m/z = 315.1 [M-C ₄ H ₈ +H] ⁺ . ¹ H NMR (400 MHz, METHANOL-d4) δ = 9.17 (s, 1H), 8.49 (dd, J = 1.5, 8.3 Hz, 1H), 7.95 (d, J = 8.3 Hz, 1H), 4.11 - 3.99 (m, 3H), 3.84 (s, 2H), 2.65 - 2.48 (m, 4H), 1.43 (s, 9H). Note that regioisomer was generated concurrently: tert-butyl 6-[2-(trifluoromethyl)pyridine-4- carbonyl]-2-azaspiro[3.3]heptane-2-carboxylate (1100 mg, 2.97 mmol, 20 % yield) as a brown oil. ¹ H NMR (400 MHz, METHANOL-d4) δ = 8.92 (d, J = 5.0 Hz, 1H), 8.15 (s, 1H), 8.04 (dd, J = 1.1, 4.9 Hz, 1H), 4.03 (s, 3H), 3.83 (s, 2H), 2.55 (br dd, J = 8.3, 12.1 Hz, 4H), 1.43 (s, 9H). Step 2: 6-[difluoro-[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspir o[3.3]heptane-2-carboxylic acid tert-butyl ester To a solution of tert-butyl 6-[6-(trifluoromethyl)pyridine-3-carbonyl]-2-azaspiro[3.3]he ptane-2- carboxylate (750 mg, 2.03 mmol) in DCM (5 mL) was added DAST (5 mL, 37.8 mmol) dropwise at 0 °C under N2 atmosphere. The reaction mixture was stirred at 25 °C for 12 h. The reaction mixture was added dropwise to saturated NaHCO ₃ aqueous solution (200 mL) and extracted with DCM (50 mL x 2). The combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by prep-HPLC (water(FA)-ACN, 58%- 88%); to afford the title compound (510 mg, 1.3 mmol, 64 % yield) as a light yellow solid. MS (ESI): m/z = 337.0 [M-C ₄ H ₈ +H] ⁺ ; ¹ H NMR (400 MHz, METHANOL-d4) δ = 8.87 (s, 1H), 8.26 - 8.13 (m, 1H), 7.94 (d, J = 8.3 Hz, 1H), 4.03 - 3.83 (m, 4H), 3.18 - 2.96 (m, 1H), 2.47 - 2.27 (m, 4H), 1.44 (s, 9H). In analogy to Building Block P.143, the following building blocks were generated using the relevant heteroarylbromide. In some cases, alternative salts (e.g. trifluoroacetate, ditosylate, hydrochloride) were also used. Building Block P.139 and P.140: 6-[(1R)-1-[4-methyl-5-(trifluoromethyl)-2-pyridyl]ethyl]- 2-azaspiro[3.3]heptane; 4-methylbenzenesulfonic acid and 6-[(1S)-1-[4-methyl-5- (trifluoromethyl)-2-pyridyl]ethyl]-2-azaspiro[3.3]heptane; 4-methylbenzenesulfonic acid (arbitrary assignment of enantiomers) The solution of tert-butyl 6-[(1R)-1-[4-methyl-5-(trifluoromethyl)-2-pyridyl]ethyl]-2- azaspiro[3.3]heptane-2-carboxylate (250 mg, 0.65 mmol) and p-toluenesulfonic acid monohydrate (309 mg, 1.63 mmol) in EtOAc (10 mL) was stirred at 60 °C for 3 h. After cooling to RT, the obtained precipitate was filtered, washed with EtOAc and dried in vacuum to give the title compound P.139 (237 mg, 0.38 mmol, 55% yield) as white solid. MS (ESI): m/z =285.2 [M+H] ⁺ . Deprotection of the other enantiomer carried out in analogy to yield title compound P.140 (241 mg, 0.38 mmol, 58 % yield) as white solid. MS (ESI): m/z =285.2 [M+H] ⁺ . Step 1: tert-butyl 6-[1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethylidene ]-2- azaspiro[3.3]heptane-2-carboxylate To a stirred -30 °C solution of 2,2,6,6-tetramethylpiperidine (4.31 mL, 25.6 mmol) in THF (75 mL) under Ar, n-BuLi (2.5 M in hexane) (10.2 mL, 25.6 mmol) was added. The solution was stirred at -30 °C for 30 min and cooled to -78 °C. The solution of 4,4,5,5-tetramethyl-2-[1- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethyl]-1,3,2-di oxaborolane (6.61 g, 23.4 mmol, CAS 1227056-25-8) in 10 mL of dry THF was added dropwise and reaction mixture was stirred at -78 °C for 30 min. A solution of tert-butyl 6-oxo-2-azaspiro[3.3]heptane-2-carboxylate (4.5 g, 21.3 mmol) in 15 mL of dry THF was added dropwise at -78 °C and reaction mixture was allowed to warm and stirred overnight at room temperature. The reaction was quenched with water and the mixture was concentrated in vacuo. The residue was separated between water and DCM. The organic layer was washed with citric acid, water, brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography (1:4 TBME/hexane) to give the title compound (3.1 g, 8.88 mmol, 41% yield) as a white solid. MS (ESI): m/z =294.2 [M-C ₄ H ₈ +H] ⁺ . Step 2: tert-butyl 6-[1-[4-methyl-5-(trifluoromethyl)-2-pyridyl]ethylidene]-2- azaspiro[3.3]heptane-2-carboxylate To a stirred suspension of 2-chloro-4-methyl-5-(trifluoromethyl)pyridine (1.36 g, 6.93 mmol, CAS 780802-36-0), tert-butyl 6-[1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethylidene ]-2- azaspiro[3.3]heptane-2-carboxylate (2.2 g, 6.3 mmol) and cesium carbonate (4.1 g, 12.6 mmol) in dry 1,4-dioxane (110 mL), 1,1'-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (771 mg, 0.94 mmol, CAS 95464-05-4) was added. The mixture was stirred at 80 °C for 48 h under argon atmosphere. After cooling to RT, the reaction mixture was filtered and concentrated in vacuo. The obtained residue was partitioned between EtOAc and brine. The organic layer was dried over Na2SO4 and concentrated to give crude product, which was purified by column chromatography (hexane/MTBE 10-23%) to obtain the title compound (700 mg, 1.83 mmol, 28% yield) as light yellow solid. MS (ESI): m/z =327.2 [M-C ₄ H ₈ +H] ⁺ . Step 3: tert-butyl 6-[1-[4-methyl-5-(trifluoromethyl)-2-pyridyl]ethyl]-2-azaspi ro[3.3]heptane-2- carboxylate The stirred mixture of tert-butyl 6-[1-[4-methyl-5-(trifluoromethyl)-2-pyridyl]ethylidene]-2- azaspiro[3.3]heptane-2-carboxylate (700 mg, 1.83 mmol) and Pd/C (5%) (200 mg) in EtOAc (50 mL) was hydrogenated in autoclave at 15200 mmHg (20 bar) for 24 h at 25 °C. The reaction mixture was filtered and concentrated in vacuo to give the title compound (680 mg, 1.77 mmol, 92% yield) as orange gum; MS (ESI): m/z =329.0 [M-C4H8+H] ⁺ . The mixture of enantiomers tert-butyl 6-[1-[4-methyl-5-(trifluoromethyl)-2-pyridyl]ethyl]-2-azaspi ro[3.3]heptane-2- carboxylate (680 mg, 1.77 mmol) was separated by chiral chromatography to give tert-butyl 6- [(1S)-1-[4-methyl-5-(trifluoromethyl)-2-pyridyl]ethyl]-2-aza spiro[3.3]heptane-2-carboxylate (270 mg, 0.7 mmol, 40% yield) (or enantiomer) RetTime (min): 11.2 and tert-butyl 6-[(1R)-1-[4- methyl-5-(trifluoromethyl)-2-pyridyl]ethyl]-2-azaspiro[3.3]h eptane-2-carboxylate (250 mg, 0.65 mmol, 37% yield) (or enantiomer) RetTime(min): 13.9. Building Block P.146: 2-(2-azaspiro[3.3]heptan-6-ylmethyl)-5-(trifluoromethyl)-7H- pyrrolo[2,3-d]pyrimidine;4-methylbenzenesulfonic acid To a solution of tert-butyl 6-[[5-(trifluoromethyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]meth yl]-2- azaspiro[3.3]heptane-2-carboxylate (48 mg, 1.1 mmol, 1 eq) in EtOAc (9.8 mL), p- toluenesulfonic acid monohydrate (749 mg, 4 mmol, 3.5 eq) was added. The mixture was stirred at 25 °C for 18 h. The reaction mixture concentrated in vacuo and residue was treated with MTBE. The formed precipitate was filtered to give 2-(2-azaspiro[3.3]heptan-6-ylmethyl)-5- (trifluoromethyl)-7H-pyrrolo[2,3-d]pyrimidine;4-methylbenzen esulfonic acid (729 mg, 1.14 mmol, 99% yield) as light yellow solid. MS (ESI): m/z = 297.2 [M+H] ⁺ . Step 1: tert-butyl 6-(7H-pyrrolo[2,3-d]pyrimidin-2-ylmethylene)-2-azaspiro[3.3] heptane-2- carboxylate To a solution of tert-butyl 6-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]-2 - azaspiro[3.3]heptane-2-carboxylate (2.2 g, 6.6 mmol, 1.01 eq, CAS 2763647-64-7) and 2- chloro-7H-pyrrolo[2,3-d]pyrimidine (1g, 6.51 mmol, 1 eq, CAS 335654-06-3), K2CO3 (2.7g, 19.54 mmol, 3 eq) in 1,4-dioxane (10 mL) and water (2 mL) was added 1,1'- bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (531mg, 0.65 mmol, 0.1 eq, CAS 95464-05-4). The mixture was stirred at 80 °C under N2 balloon (760 mmHg) for 12 h. The reaction mixture was concentrated in vacuo and purified by column chromatography (SiO ₂ , petroleum ether/Ethyl acetate=2/1 to 1/1) to afford tert-butyl 6-(7H- pyrrolo[2,3-d]pyrimidin-2-ylmethylene)-2-azaspiro[3.3]heptan e-2-carboxylate (650mg, 1.99 mmol, 27% yield) as a pink solid. MS (ESI): m/z = 327.2 [M+H] ⁺ . Step 2: tert-butyl 6-(7H-pyrrolo[2,3-d]pyrimidin-2-ylmethyl)-2-azaspiro[3.3]hep tane-2- carboxylate To a solution of tert-butyl 6-(7H-pyrrolo[2,3-d]pyrimidin-2-ylmethylene)-2- azaspiro[3.3]heptane-2-carboxylate (650 mg, 1.99 mmol, 1 eq) in EtOAc (10 mL) was added wet Pd/C (100 mg, 0.6 mmol, 0.3 eq) under N ₂ . The suspension was degassed under vacuum and purged with H2. The reaction was stirred under H2(15 psi) at 25 °C for 1 h to give a black suspension. The precipitate was filtered off and the filtrate was dried in vacuo to afford tert-butyl 6-(7H-pyrrolo[2,3-d]pyrimidin-2-ylmethyl)-2-azaspiro[3.3]hep tane-2-carboxylate (450 mg, 1.37 mmol, 68% yield) as yellow solid. MS (ESI): m/z = 329.3 [M+H] ⁺ . Step 3: tert-butyl 6-[(5-iodo-7H-pyrrolo[2,3-d]pyrimidin-2-yl)methyl]-2-azaspir o[3.3]heptane- 2-carboxylate To a solution of tert-butyl 6-(7H-pyrrolo[2,3-d]pyrimidin-2-ylmethyl)-2-azaspiro[3.3]hep tane-2- carboxylate (650 mg, 1.98 mmol, 1 eq) in ACN (20 mL) was added NIS (534 mg, 2.38 mmol, 1.2 eq) and the reaction mixture was stirred at 25 °C for 2 h to give a yellow suspension. The reaction mixture was added to water (20 ml) and the mixture was filtered. The cake was concentrated in vacuo to give the tert-butyl 6-[(5-iodo-7H-pyrrolo[2,3-d]pyrimidin-2-yl)methyl]- 2-azaspiro[3.3]heptane-2-carboxylate (700 mg, 1.54 mmol, 75% yield) as a yellow solid. MS (ESI): m/z = 455.1 [M+H] ⁺ . Step 4: tert-butyl 6-[[5-iodo-7-(p-tolylsulfonyl)pyrrolo[2,3-d]pyrimidin-2-yl]m ethyl]-2- azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[(5-iodo-7H-pyrrolo[2,3-d]pyrimidin-2-yl)methyl]-2- azaspiro[3.3]heptane-2-carboxylate (700 mg, 1.54 mmol, 1 eq) in THF (5 mL) was added NaH (74 mg, 1.85 mmol, 1.2 eq) at 0 °C. The mixture was stirred at 0 °C for 0.5 h.4- methylbenzenesulfonyl chloride (587 mg, 3.08 mmol, 2 eq) was added. The mixture was stirred at 25 °C for 12 h to give a grey suspension. The reaction mixture was quenched by addition aq.sat.NH4Cl 10 mL at 0 °C and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude material and was purified by column chromatography on silica gel eluted with PE/EtOAc (PE/EtOAc = 3 : 1) to give tert-butyl 6-[[5-iodo-7-(p-tolylsulfonyl)pyrrolo[2,3-d]pyrimidin-2-yl]m ethyl]-2- azaspiro[3.3]heptane-2-carboxylate (900 mg, 1.48 mmol, 96% yield) as a light yellow soild. MS (ESI): m/z = 455.1 [M+H] ⁺ . Step 5: tert-butyl 6-[[5-(trifluoromethyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]meth yl]-2- azaspiro[3.3]heptane-2-carboxylate To a solution of benzyl tert-butyl 6-[[5-iodo-7-(p-tolylsulfonyl)pyrrolo[2,3-d]pyrimidin-2- yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (900 mg, 1.48 mmol, 1 eq) and copper (282 mg, 4.44 mmol, 3 eq) in DMF (1 mL) was added diphenyl(trifluoromethyl)sulfonium;trifluoromethanesulfonate (1.2 g, 2.96 mmol, 2 eq, CAS 147531-11-1). The reaction mixture was stirred at 80 °C for 12 h and concentrated in vacuo. The residue was poured into water (10 mL), extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by column chromatography on silica gel eluted with PE/EtOAc = 3:1 to afford tert-butyl 6-[[7-(p-tolylsulfonyl)-5-(trifluoromethyl)pyrrolo[2,3-d]pyr imidin-2-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (300 mg, 0.54 mmol, 36% yield) as a light red oil and tert- butyl 6-[[5-(trifluoromethyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]meth yl]-2-azaspiro[3.3]heptane- 2-carboxylate (260 mg, 0.66 mmol, 44% yield) as a light brown oil. MS (ESI): m/z = 397.1 [M+H] ⁺ . Building Block P.161: 6-(2-azaspiro[3.3]heptan-6-ylmethyl)-3-(trifluoromethyl)-1,2 - benzoxazole;4-methylbenzenesulfonic acid A mixture of tert-butyl 6-[[3-(trifluoromethyl)-1,2-benzoxazol-6-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (1.4 g, 3.53 mmol, 1 eq) and p-toluenesulfonic acid monohydrate (1 g, 5.26 mmol, 1.49 eq) in EtOAc (100 mL) was stirred at 50 °C for 3 h. The reaction mixture was concentrated in vacuo and the resulting residue was stirred with TBME (100mL) for 3 h. The precipitate was filtered and dried to give 6-(2-azaspiro[3.3]heptan-6- ylmethyl)-3-(trifluoromethyl)-1,2-benzoxazole;4-methylbenzen esulfonic acid (1.31 g, 2.8 mmol, 75.21% yield) as a white solid. MS (ESI): m/z = 297.0 [M+H] ⁺ . Step 1 : tert-butyl 6-[[3-fluoro-4-(2,2,2-trifluoroacetyl)phenyl]methylene]-2- azaspiro[3.3]heptane-2-carboxylate To a stirred suspension of tert-butyl 6-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]- 2-azaspiro[3.3]heptane-2-carboxylate (3.72 g, 11.1 mmol, 1eq, CAS 2763647-64-7), 1-(4- bromo-2-fluoro-phenyl)-2,2,2-trifluoro-ethanone (3.01 g, 11.1 mmol, 1 eq, CAS 617706-18-0) and potassium carbonate (3.07 g, 22.19 mmol, 2 eq) in 1,4-dioxane (70 mL) and water (7 mL), 1,1'-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (1.36 g, 1.66 mmol, 0.15 eq, CAS 95464-05-4) was added. The mixture was stirred at 80 °C for 18 h. The reaction mixture was concentrated in vacuo. The residue was stirred with EtOAc (200 mL) and Na2SO4. The mixture was filtered and concentrated in vacuo. The crude product was purified by FC to obtain tert-butyl 6-[[3-fluoro-4-(2,2,2-trifluoroacetyl)phenyl]methylene]-2- azaspiro[3.3]heptane-2-carboxylate (2.8 g, 7.01 mmol, 58% yield) as light red solid. MS (ESI): m/z = 300.0 [M+H] ⁺ . FC conditions: Column Interchim, SiO ₂ (120g), hexane/ethyl acetate (0-27%), flow rate = 80mL/min. Step 2 : tert-butyl 6-[[3-fluoro-4-(2,2,2-trifluoroacetyl)phenyl]methyl]-2-azasp iro[3.3]heptane- 2-carboxylate To a solution of tert-butyl 6-[[3-fluoro-4-(2,2,2-trifluoroacetyl)phenyl]methylene]-2- azaspiro[3.3]heptane-2-carboxylate (3 g, 7.51 mmol, 1 eq) and in EtOAc (150 mL), Pd/C (10%) (300 mg) was added. The mixture was hydrogenated at 3800 mmHg (in autoclave) and then allowed to stirr at RT for 36 h. The reaction mixture was filtered. The filtrate was concentrated in vacuo to give tert-butyl 6-[[3-fluoro-4-(2,2,2-trifluoroacetyl)phenyl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (3.0 g, 7.47 mmol, 90% yield) as a light brown oil. MS (ESI): m/z =346.0 [M-C ₄ H ₈ +H] ⁺ . Step 3: tert-butyl 6-[[3-fluoro-4-[N-hydroxy-C-(trifluoromethyl)carbonimidoyl]p henyl]methyl]- 2-azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[[3-fluoro-4-(2,2,2-trifluoroacetyl)phenyl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (3 g, 7.47 mmol, 1 eq) in pyridine (40 mL), hydroxylamine;hydrochloride (0.93 g, 13.45 mmol, 1.8 eq) was added. The mixture was stirred at 50 °C for 18 h. The mixture was concentrated in vacuo. The residue was stirred with water (50 mL) for 2 h. The aqueous layer was decanted and the obtained residue was partitioned between TBME (100 mL) and water (15 mL). The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo with toluene to give tert-butyl 6-[[3-fluoro-4-[N-hydroxy-C- (trifluoromethyl)carbonimidoyl]phenyl]methyl]-2-azaspiro[3.3 ]heptane-2-carboxylate (2.8 g, 6.72 mmol, 80% yield). MS (ESI): m/z =361.2 [M-C ₄ H ₈ +H] ⁺ . Step 4 : tert-butyl 6-[[3-(trifluoromethyl)-1,2-benzoxazol-6-yl]methyl]-2-azaspi ro[3.3]heptane- 2-carboxylate The mixture of tert-butyl 6-[[3-fluoro-4-[N-hydroxy-C- (trifluoromethyl)carbonimidoyl]phenyl]methyl]-2-azaspiro[3.3 ]heptane-2-carboxylate (2.8 g, 6.72 mmol, 1 eq) and potassium carbonate (1.39 g, 10.09 mmol, 1.5 eq) in dry DMF (60 mL) was stirred at 80 °C for 18 h. The reaction mixture was poured into water (300 mL) and extracted with EtOAc/TBME (100mL/100mL). The organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo to give tert-butyl 6-[[3-(trifluoromethyl)-1,2- benzoxazol-6-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (1.5 g, 3.78 mmol, 53% yield). MS (ESI): m/z =341.0 [M-C ₄ H ₈ +H] ⁺ . Building Block P.162: 1-(2-azaspiro[3.3]heptan-6-ylmethyl)-4-[1- (trifluoromethyl)cyclopropyl]pyridin-2-one;4-methylbenzenesu lfonic acid To a solution of tert-butyl 6-[[2-oxo-4-[1-(trifluoromethyl)cyclopropyl]-1-pyridyl]methy l]-2- azaspiro[3.3]heptane-2-carboxylate (230 mg, 0.56 mmol, 1 eq) in EtOAc (3 mL) was added p- toluenesulfonic acid (115 mg, 0.67 mmol, 1.2 eq). The reaction was stirred at 80 °C for 12 h. The reaction mixture was concentrated in vacuo. To the residue was added deionized water (3 mL) and then lyophilized to afford 1-(2-azaspiro[3.3]heptan-6-ylmethyl)-4-[1- (trifluoromethyl)cyclopropyl]pyridin-2-one;4-methylbenzenesu lfonic acid (236 mg, 0.49 mmol, 81% yield) as a yellow solid. MS (ESI): m/z = 313.1 [M+H] ⁺ . Step 1: tert-butyl 6-[(4-bromo-2-oxo-1-pyridyl)methylene]-2-azaspiro[3.3]heptan e-2- carboxylate To a solution of 4-bromo-1H-pyridin-2-one (5 g, 28.74 mmol, 1 eq) in DCE (100 mL) was added tert-butyl 6-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]-2 - azaspiro[3.3]heptane-2-carboxylate (11.56 g, 34.48 mmol, 1.2 eq, CAS 2763647-64-7), pyridine (4.55 g, 57.47 mmol, 2 eq), boric acid (1.78 g, 28.74 mmol, 1 eq) and Cu(OAc)2 (7.75 g, 38.79 mmol, 1.35 eq). The mixture was stirred at 70 °C for 16 h under O2. The reaction mixture was concentrated in vacuo. The residue was purified by silica gel chromatography (petroleum ether/EtOAc=0:1, Rf=0.4) and concentrated in vacuo to give tert-butyl 6-[(4-bromo-2-oxo-1- pyridyl)methylene]-2-azaspiro[3.3]heptane-2-carboxylate (2.74 g, 7.19 mmol, 25% yield) as white solid. MS (ESI): m/z = 325.0 [M-C ₄ H ₈ +H] ⁺ . Step 2: tert-butyl 6-[(4-bromo-2-oxo-1-pyridyl)methyl]-2-azaspiro[3.3]heptane-2 -carboxylate To a solution of tert-butyl 6-[(4-bromo-2-oxo-1-pyridyl)methylene]-2-azaspiro[3.3]heptan e-2- carboxylate (629 mg, 1.65 mmol, 1 eq) in EtOAc (6 mL) was added PtO2 (112 mg, 0.49 mmol, 0.3 eq) under N ₂ . The suspension was degassed under vacuum and purged with H ₂ . The reaction was stirred under H2(15 psi) at 25 °C for 0.5 h. The reaction mixture was concentrated in vacuo. The residue was purified by silica gel chromatography (petroleum ether/EtOAc=60%)(petroleum ether/EtOAc=1:1, Rf=0.4) and concentrated in vacuo to give tert-butyl 6-[(4-bromo-2-oxo-1- pyridyl)methyl]-2-azaspiro[3.3]heptane-2-carboxylate (370 mg, 0.97 mmol, 58% yield) as yellow oil. MS (ESI): m/z = 327.0 [M-C4H8+H] ⁺ . Step 3: tert-butyl 6-[[2-oxo-4-[1-(trifluoromethyl)vinyl]-1-pyridyl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[(4-bromo-2-oxo-1-pyridyl)methyl]-2-azaspiro[3.3]heptane-2 - carboxylate (300 mg, 0.78 mmol, 1 eq) and 4,4,6-trimethyl-2-[1-(trifluoromethyl)vinyl]-1,3,2- dioxaborinane (208 mg, 0.94 mmol, 1.2 eq, CAS 1011460-68-6), K ₂ CO ₃ (324 mg, 2.35 mmol, 3 eq) in 1,4-dioxane (3 mL) and water (0.600 mL) was added 1,1'- bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (63.87 mg, 0.08 mmol, 0.1 eq, CAS 95464-05-4). The mixture was degassed with N ₂ and stirred at 80 °C under N ₂ atmosphere for 12 h. The reaction mixture was concentrated in vacuo. The residue was purified by silica gel chromatography (petroleum ether/EtOAc=60%)(petroleum ether/EtOAc=1:1, Rf=0.4) and concentrated in vacuo to give tert-butyl 6-[[2-oxo-4-[1- (trifluoromethyl)vinyl]-1-pyridyl]methyl]-2-azaspiro[3.3]hep tane-2-carboxylate (360 mg, 0.9 mmol, 115% yield) yellow oil. MS (ESI): m/z = 343.1 [M-C ₄ H ₈ +H] ⁺ . Step 4: tert-butyl 6-[[2-oxo-4-[1-(trifluoromethyl)cyclopropyl]-1-pyridyl]methy l]-2- azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[[2-oxo-4-[1-(trifluoromethyl)vinyl]-1-pyridyl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (320 mg, 0.8 mmol, 1 eq) in THF (3 mL) was added diphenyl(methyl)sulfonium tetrafluoroborate (323 mg, 1.12 mmol, 1.4 eq, CAS 10504-60-6). NaHMDS/THF (1.36 mL, 1.36 mmol, 1.69 eq) was added dropwise at 0 °C. The reaction mixture was stirred at 25 °C for 1 h under N2 atmosphere. The reaction mixture was slowly added to 6 mL sat. aq NH4Cl. The mixture was added to 6 mL water and extracted with EtOAc (4 mL x 3). The organic phases were concentrated in vacuo. The crude product was purified by chromatography on silica gel (PE:EtOAc=0:1) to give tert-butyl 6-[[2-oxo-4-[1- (trifluoromethyl)cyclopropyl]-1-pyridyl]methyl]-2-azaspiro[3 .3]heptane-2-carboxylate (250.0 mg, 0.61 mmol, 75% yield) as yellow solid. MS (ESI): m/z = 357.1 [M-C4H8+H] ⁺ . In analogy to Building Block P.162, the following building blocks were generated using the relevant heteroaryl compound for the Chan Lam-type coupling in Step 1. Building Block P.164: 5-(2-azaspiro[3.3]heptan-6-ylmethyl)-3-[1- (trifluoromethyl)cyclopropyl]-1,2,4-oxadiazole;2,2,2-trifluo roacetic acid To a solution of 6-[[3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-5-yl] methyl]-2- azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (130 mg, 335 µmol, 1 eq) in dichloromethane (1 mL) was added TFA (382 mg, 258.53 uL, 3.36 mmol, 10 eq). The reaction mixture was stirred at RT for 18 h. The rection mixture was concentrated in vacuo to give 5-(2- azaspiro[3.3]heptan-6-ylmethyl)-3-[1-(trifluoromethyl)cyclop ropyl]-1,2,4-oxadiazole;2,2,2- trifluoroacetic acid (324 mg, 241% yield). MS (ESI): m/z = 288.2 [M+H] ⁺ . Step 1: tert-butyl 6-[2-[(Z)-[amino-[1-(trifluoromethyl)cyclopropyl]methylene]a mino]oxy-2- oxo-ethyl]-2-azaspiro[3.3]heptane-2-carboxylate A solution of 2-(2-tert-butoxycarbonyl-2-azaspiro[3.3]heptan-6-yl)acetic acid (2.5 g, 9.79 mmol, 1 eq, CAS 1251002-39-7) and CDI (1905 mg, 11.75 mmol, 1.2 eq) in DMF (30 mL) was stirred at room temperature for 3 h. N'-hydroxy-1-(trifluoromethyl)cyclopropanecarboxamidine (1.64 g, 9.79 mmol, 1 eq, CAS 2172624-76-7) was added. The solution was stirred at 25 °C for 2 h. The reaction mixture was purified by reversed-phase HPLC (condition: water(0.02% FA),ACN ) to afford tert-butyl 6-[2-[(Z)-[amino-[1-(trifluoromethyl)cyclopropyl]methylene]a mino]oxy-2-oxo- ethyl]-2-azaspiro[3.3]heptane-2-carboxylate (1.5 g, 3.7 mmol, 37% yield) as a white solid. MS (ESI): m/z = 350.1 [M-C ₄ H ₈ +H] ⁺ . Step 2: tert-butyl 6-[[3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-5-yl] methyl]-2- azaspiro[3.3]heptane-2-carboxylate A mixture of tert-butyl 6-[2-[(Z)-[amino-[1-(trifluoromethyl)cyclopropyl]methylene]a mino]oxy- 2-oxo-ethyl]-2-azaspiro[3.3]heptane-2-carboxylate (1.5 g, 3.7 mmol, 1 eq) and tetrabutylammonium fluoride/THF (1.85 mL, 1.85 mmol, 0.5 eq) in THF (20 mL) was stirred at 70 °C for 1 h. The reaction mixture was concentrated in vacuo. The residue was purified by prep-HPLC( FA conditions: water(FA)-ACN,Phenomenex luna C18150*40mm* 15um) and lyophilized to give tert-butyl 6-[[3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-5- yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (807 mg, 2.08 mmol, 56.3% yield) as a light yellow solid. MS (ESI): m/z = 388.1 [M+H] ⁺ . Building Block P.165: 3-(2-azaspiro[3.3]heptan-6-ylmethyl)-5-[1- (trifluoromethyl)cyclopropyl]-1,2,4-oxadiazole;4-methylbenze nesulfonic acid To a solution of tert-butyl 6-[[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-3-yl] methyl]- 2-azaspiro[3.3]heptane-2-carboxylate (370 mg, 0.96 mmol, 1 eq) in EtOAc (4 mL) was added p- toluenesulfonic acid (197 mg, 1.15 mmol, 1.2 eq). The mixture was stirred at 80 °C for 12 h. The reaction mixture was concentrated in vacuo. To the residue was added deionized water (3 mL) and then lyophilized to afford 3-(2-azaspiro[3.3]heptan-6-ylmethyl)-5-[1- (trifluoromethyl)cyclopropyl]-1,2,4-oxadiazole;4-methylbenze nesulfonic acid (406 mg, 0.88 mmol, 82% yield) as white solid. MS (ESI): m/z = 288.1 [M+H] ⁺ . Step 1: tert-butyl 6-(cyanomethyl)-2-azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-(cyanomethylene)-2-azaspiro[3.3]heptane-2-carboxylate (2.66 g, 11.35 mmol, 1 eq, CAS 1428726-12-8) in methanol (26 mL) was added Pd/C(wet) (886 mg, 1.14 mmol, 0.1 eq) at 25 °C. The reaction was stirred at 25 °C under H2 atmosphere(H2 balloon) for 0.5 h. The reaction mixture was filtered and the filtrate was concentrated in vacuo to give tert-butyl 6-(cyanomethyl)-2-azaspiro[3.3]heptane-2-carboxylate (2.6 g, 11.0 mmol, 96% yield) as white solid. MS (ESI): m/z = 181.0 [M-C4H8+H] ⁺ . Step 2: tert-butyl 6-[(2Z)-2-amino-2-hydroxyimino-ethyl]-2-azaspiro[3.3]heptane -2-carboxylate To a mixture of hydroxylamine;hydrochloride (588 mg, 8.46 mmol, 2 eq) in ethanol (10 mL) was added triethylamine (856 mg, 8.46 mmol, 2 eq) at 25 °C. After 0.5 h, tert-butyl 6- (cyanomethyl)-2-azaspiro[3.3]heptane-2-carboxylate (1 g, 4.23 mmol, 1 eq) was added. The reaction was stirred at 50 °C for 2 h. The reaction was concentrated in vacuo. The residue was dissolve in water (10 mL), extracted with ethyl acetate (5 mL x 3). The combined extracts were concentrated in vacuo to give tert-butyl 6-[(2Z)-2-amino-2-hydroxyimino-ethyl]-2- azaspiro[3.3]heptane-2-carboxylate (1.03 g, 3.82 mmol, 90% yield) as colorless oil. MS (ESI): m/z = 270.2 [M+H] ⁺ . Step 3: tert-butyl 6-[(2Z)-2-amino-2-[1-(trifluoromethyl)cyclopropanecarbonyl]o xyimino-ethyl]- 2-azaspiro[3.3]heptane-2-carboxylate A solution of 1-(trifluoromethyl)cyclopropane-1-carboxylic acid (589 mg, 3.82 mmol, 1 eq, CAS 277756-46-4) and CDI (744 mg, 4.59 mmol, 1.2 eq) in DMF (10 mL) was stirred at room temperature for 2 h. tert-Butyl 6-[(2Z)-2-amino-2-hydroxyimino-ethyl]-2-azaspiro[3.3]heptane - 2-carboxylate (1.03 g, 3.82 mmol, 1 eq) was added to the solution and stirred at 25 °C for 1 h. The reaction mixture was purified by reversed-phase HPLC (condition: water(0.02% FA),ACN ) to afford tert-butyl 6-[(2Z)-2-amino-2-[1-(trifluoromethyl)cyclopropanecarbonyl]o xyimino- ethyl]-2-azaspiro[3.3]heptane-2-carboxylate (130 mg, 0.32 mmol, 8.4% yield) as a white solid. MS (ESI): m/z = 350.1 [M-C4H8+H] ⁺ . Step 4: tert-butyl 6-[[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-3-yl] methyl]-2- azaspiro[3.3]heptane-2-carboxylate A solution of tert-butyl 6-[2-[(Z)-[amino-[1-(trifluoromethyl)cyclopropyl]methylene]a mino]oxy- 2-oxo-ethyl]-2-azaspiro[3.3]heptane-2-carboxylate (210 mg, 0.52 mmol, 1 eq) and tetrabutylammonium fluoride/THF (0.13 mL, 0.13 mmol, 0.25 eq) in THF (2 mL) was stirred at 70 °C for 1 h. The mixture was added to 2 mL water and extracted with EtOAc (15 mL x 3). The organic phases were concentrated in vacuo. The mixture was purified by PREP-HPLC to give tert-butyl 6-[[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-3-yl] methyl]-2- azaspiro[3.3]heptane-2-carboxylate (220 mg, 0.57 mmol, 109% yield) as yellow solid. MS (ESI): m/z = 332.1 [M-C4H8+H] ⁺ . Building Block P.167: 4-methylbenzenesulfonic acid;6-[[5-[1- (trifluoromethyl)cyclopropyl]imidazol-1-yl]methyl]-2-azaspir o[3.3]heptane To a solution of tert-butyl 6-[[5-[1-(trifluoromethyl)cyclopropyl]imidazol-1-yl]methyl]- 2- azaspiro[3.3]heptane-2-carboxylate (300 mg, 0.78 mmol, 1 eq) in EtOAc (6 mL) was added p- toluenesulfonic acid monohydrate (444 mg, 2.34 mmol, 3 eq). The mixture was stirred at 30 °C for 72 h. The reaction mixture was concentrated in vacuo. The residue was purified by HPLC to give 4-methylbenzenesulfonic acid;6-[[5-[1-(trifluoromethyl)cyclopropyl]imidazol-1- yl]methyl]-2-azaspiro[3.3]heptane (81 mg, 0.13 mmol, 15% yield) as yellow gum. MS (ESI): m/z = 286.2 [M+H] ⁺ . HPLC conditions: Device (Mobile Phase, Column) : SYSTEM 0-2-9 min 0-70% H20/MEOH/0.1NH4OH flow 30 ml/min ((loading pump 4 ml MEOH) target mass337 column : XBridge BEH C18100*19mm,5 microM. Step 1: 4-[1-(trifluoromethyl)cyclopropyl]-1H-imidazole 2-bromo-1-[1-(trifluoromethyl)cyclopropyl]ethanone (0.5 g, 2.16 mmol, 1 eq, CAS 1382999-80- 5) was added to methanamide (5 mL, 125 mmol, 58 eq). The reaction mixture was stirred at 180 °C for 2 h. After the reaction was completed, 50 mL of water was added. The mixture was washed three times with dichloromethane, then the aqueous phase was adjusted to pH 8 with a 1 M aqueous NaOH solution. The aqueous phase was extracted twice with dichloromethane. The organic phase was dried, concentrated in vacuo and purified by HPLC to give 4-[1- (trifluoromethyl)cyclopropyl]-1H-imidazole (110 mg, 0.62 mmol, 28% yield) as brown solid. MS (ESI): m/z = 177.2 [M+H] ⁺ . HPLC conditions: Device (Mobile Phase, Column) : SYSTEM 0-2-10 min0-75% H20/ACN, flow 30 ml/min ((loading pump 4 mACN) target mass177 column : Chromatorex C18 SMB100-5T 100*19mm, 5 micro. Step 2: tert-butyl 6-[[5-[1-(trifluoromethyl)cyclopropyl]imidazol-1-yl]methyl]- 2- azaspiro[3.3]heptane-2-carboxylate To a mixture of 4-[1-(trifluoromethyl)cyclopropyl]-1H-imidazole (800 mg, 3.41 mmol, 1 eq), cesium carbonate (2.21 g, 6.81 mmol, 2 eq) in DMF (15 mL) was added tert-butyl 6- (methylsulfonyloxymethyl)-2-azaspiro[3.3]heptane-2-carboxyla te (1.04 g, 3.41 mmol, 1 eq, CAS 2740574-92-7) at room temperature. The reaction mixture was stirred at 50 °C for 18 h. The reaction mixture was diluted with EtOAc (100ml) and washed with water (2 x 200ml), brine (100ml). The organics layers were separated, dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by FC to give tert-butyl 6-[[4-[1- (trifluoromethyl)cyclopropyl]imidazol-1-yl]methyl]-2-azaspir o[3.3]heptane-2-carboxylate (800 mg, 2.07 mmol, 60% yield) and tert-butyl 6-[[5-[1-(trifluoromethyl)cyclopropyl]imidazol-1- yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (300 mg, 0.78 mmol, 22% yield) as light yellow solid. MS (ESI): m/z = 286.2 [M+H] ⁺ . FC conditions: Interchim; 40g SiO ₂ , petroleum ether/MtBE with MtBE from 15~100%, further MtBE/methanol with methanol from 0~10% flow rate = 40 mL/min, Rv = 21-23 CV. Building Block P.168: 6-[difluoro-[6-(trifluoromethyl)pyridazin-3-yl]methyl]-2- azaspiro[3.3]heptane;4-methylbenzenesulfonic acid To a solution of tert-butyl 6-[difluoro-[6-(trifluoromethyl)pyridazin-3-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (3.38 g, 8.59 mmol, 1 eq) in EtOAc (34 mL) was added p- toluenesulfonic acid (1.77 g, 10.3 mmol, 1.2 eq). The reaction was stirred at 80 °C for 4 h. The reaction mixture was concentrated in vacuo. To the residue was added deionized water (30 mL) and lyophilized to afford 6-[difluoro-[6-(trifluoromethyl)pyridazin-3-yl]methyl]-2- azaspiro[3.3]heptane;4-methylbenzenesulfonic acid (3.96 g, 8.51 mmol, 97% yield) as yellow solid. MS (ESI): m/z = 294.3 [M+H] ⁺ . Step 1: tert-butyl 6-[[6-(trifluoromethyl)pyridazin-3-yl]methylene]-2-azaspiro[ 3.3]heptane-2- carboxylate To a solution of 3-chloro-6-(trifluoromethyl)pyridazine (30 g, 164 mmol, 1 eq, CAS 258506-68- 2) in 1,4-dioxane (500 mL) and water (50 mL) was added tert-butyl 6-[(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)methylene]-2-azaspiro[3.3]heptane-2- carboxylate (55.1 g, 164 mmol, 1 eq, CAS 2763647-64-7), potassium carbonate (45.43 g, 328 mmol, 2 eq) and1,1'- bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (13.41 g, 16.44 mmol, 0.1 eq, CAS 95464-05-4). The reaction mixture was stirred at 100 °C for 12 h under N2 atmosphere. The reaction mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with PE/EtOAc (3:1) (TLC, PE: EtOAc=3:1, Rf=0.40) to afford the crude product. The crude product was washed with PE (300 mL). After filtration, the solids were collected and concentrated in vacuo to afford tert-butyl 6-[[6-(trifluoromethyl)pyridazin-3-yl]methylene]-2-azaspiro[ 3.3]heptane-2- carboxylate (46 g, 121 mmol, 73% yield) as yellow solid. MS (ESI): m/z =300.3 [M-C ₄ H ₈ +H] ⁺ . Step 2: tert-butyl 6-[[6-(trifluoromethyl)pyridazin-3-yl]methyl]-2-azaspiro[3.3 ]heptane-2- carboxylate To a solution of tert-butyl 6-[[6-(trifluoromethyl)pyridazin-3-yl]methylene]-2- azaspiro[3.3]heptane-2-carboxylate (19 g, 53.47 mmol, 1 eq) in EtOAc (600 mL) was added Pd/C(wet) (6.33 g, 5.95 mmol, 0.11 eq) at 25 °C. The reaction was stirred at 25 °C under H2 atmosphere (H2 balloon) for 1 h. The reaction mixture was filtered and the filtrate was concentrated in vacuo to afford tert-butyl 6-[[6-(trifluoromethyl)pyridazin-3-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate (19 g, 53.17 mmol, 99% yield) as a yellow solid. MS (ESI): m/z = 358.2 [M+H] ⁺ . Step 3: tert-butyl 6-[6-(trifluoromethyl)pyridazine-3-carbonyl]-2-azaspiro[3.3] heptane-2- carboxylate To a solution of tert-butyl 6-[[6-(trifluoromethyl)pyridazin-3-yl]methyl]-2-azaspiro[3.3 ]heptane- 2-carboxylate (15 g, 41.9 mmol, 1 eq) in 1,4-dioxane (300 mL) was added SeO2 (27.94 g, 251.8 mmol, 6 eq). The reaction mixture was stirred at 90 °C for 12 h under N2 atmosphere. The reaction mixture was filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent of 0~30% AcOEt/petroleum ether, petroleum ether/AcOEt=1/1, Rf=0.5) and concentrated in vacuo to give tert-butyl 6-[6-(trifluoromethyl)pyridazine-3-carbonyl]-2- azaspiro[3.3]heptane-2-carboxylate (4.3 g, 11.58 mmol, 27% yield) as yellow solid. MS (ESI): m/z =316.0 [M-C4H8+H] ⁺ . Step 4: tert-butyl 6-[difluoro-[6-(trifluoromethyl)pyridazin-3-yl]methyl]-2- azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[6-(trifluoromethyl)pyridazine-3-carbonyl]-2-azaspiro[3.3] heptane- 2-carboxylate (3 g, 8.08 mmol, 1 eq) in DCM (30 mL) was added DAST (30 mL, 227 mmol, 28 eq) dropwise at 0 °C under N2 atmosphere. The reaction mixture was stirred at 25 °C for 12 h. The reaction mixture was added dropwise to saturated NaHCO ₃ aqueous solution (500 mL) and extracted with EtOAc (200 mL x 3). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with PE/EtOAc (5:1) (TLC, PE: EtOAc=3:1, Rf=0.40) to afford tert-butyl 6- [difluoro-[6-(trifluoromethyl)pyridazin-3-yl]methyl]-2-azasp iro[3.3]heptane-2-carboxylate (2.6 g, 6.61 mmol, 81.82% yield) as yellow solid. MS (ESI): m/z = 394.0 [M+H] ⁺ . In analogy to Building Block P.168, the following building blocks were generated using the relevant heteroarylbromide or heteroarylchloride for the cross coupling in Step 1. Building Block P.178: 6-(2-azaspiro[3.3]heptan-6-ylmethyl)-2- (trifluoromethyl)imidazo[1,2-a]pyrimidine;4-methylbenzenesul fonic acid A mixture of p-toluenesulfonic acid (364 mg, 2.12 mmol, 3 eq) and tert-butyl 6-[[2- (trifluoromethyl)imidazo[1,2-a]pyrimidin-6-yl]methyl]-2-azas piro[3.3]heptane-2-carboxylate (280 mg, 0.71 mmol, 1 eq) in EtOAc (30 mL) was stirred at 50 °C for 24 h. The mixture was concentrated in vacuo and purificated by FC to afford 6-(2-azaspiro[3.3]heptan-6-ylmethyl)-2- (trifluoromethyl)imidazo[1,2-a]pyrimidine;4-methylbenzenesul fonic acid (178 mg, 0.38 mmol, 53% yield) as a light brown solid. MS (ESI): m/z = 297.0 [M+H] ⁺ . FC conditions: Interchim, 40 g SiO2, MTBE / methanol (0-60%), flow rate = 40 ml/min, 16,1- 18,3 CV. Step 1: tert-butyl 6-[(2-aminopyrimidin-5-yl)methylene]-2-azaspiro[3.3]heptane- 2-carboxylate 1,1'-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (1.87 g, 2.3 mmol, 0.2 eq, CAS 95408-45-0), potassium carbonate (3.17 g, 22.99 mmol, 2.0 eq), 2- amino-5-bromopyrimidine (2 g, 11.49 mmol, 1 eq) and tert-butyl 6-[(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)methylene]-2-azaspiro[3.3]heptane-2-carbox ylate (3.85 g, 11.49 mmol, 1 eq, CAS 2763647-64-7) were added to a mixture of 1,4-dioxane (61 mL) and water (13 mL). The reaction mixture was stirred at 90 °C for 24 h. The reaction mixture was concentrated in vacuo. The residue was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by FC to give tert-butyl 6-[(2-aminopyrimidin-5-yl)methylene]-2-azaspiro[3.3]heptane- 2-carboxylate (1.5 g, 4.96 mmol, 43% yield) as a light yellow solid. MS (ESI): m/z = 303.2 [M+H] ⁺ . FC conditions: Interchim, 120 g SiO2, chloroform/acetonitrile (0-100%), flow rate = 80 ml/min, 22,6-28,3 CV. Step 2: tert-butyl 6-[(2-aminopyrimidin-5-yl)methyl]-2-azaspiro[3.3]heptane-2-c arboxylate A mixture of tert-butyl 6-[(2-aminopyrimidin-5-yl)methylene]-2-azaspiro[3.3]heptane- 2- carboxylate (1.5 g, 4.96 mmol, 1 eq) and Pd/C, 10% (158 mg, 0.15 mmol, 0.03 eq) in EtOAc (80 mL) was hydrogenated at 19000 mmHg and stirred at 25 °C for 18 h. The reaction mixture was filtered and concentrated in vacuo to afford tert-butyl 6-[(2-aminopyrimidin-5-yl)methyl]-2- azaspiro[3.3]heptane-2-carboxylate (1.5 g, 4.93 mmol, 96% yield) as white solid. MS (ESI): m/z = 249.2 [M-C ₄ H ₈ +H] ⁺ . Step 3: tert-butyl 6-[[2-(trifluoromethyl)imidazo[1,2-a]pyrimidin-6-yl]methyl]- 2- azaspiro[3.3]heptane-2-carboxylate A solution of tert-butyl 6-[(2-aminopyrimidin-5-yl)methyl]-2-azaspiro[3.3]heptane-2- carboxylate (1.5 g, 4.93 mmol, 1 eq) and 3-bromo-1,1,1-trifluoroacetone (940 mg, 4.93 mmol, 1 eq) in ACN (9 mL) and toluene (1.5 mL) was stirred at 100 °C for 24 h. The reaction mixture concentrated in vacuo and diluted between DCM and NaHCO3 (10% aq solution). The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The crude product was purified by FC to afford tert-butyl 6-[[2-(trifluoromethyl)imidazo[1,2-a]pyrimidin-6-yl]methyl]- 2- azaspiro[3.3]heptane-2-carboxylate (340.0 mg, 0.86 mmol, 17% yield) as yellow solid. MS (ESI): m/z = 397.2 [M+H] ⁺ . FC conditions: Interchim: 40g SiO2, chloroform/ACN with ACN from 0~40%, flow rate =40mL/min, Rv =10-12 CV. Synthesis of non-commercial building blocks: C.184 tert-Butyl 2-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]-7 - azaspiro[3.5]nonane-7-carboxylate 2,2,6,6-tetramethylpiperidine (16 mL, 100 mmol, 1.2 eq, CAS 768-66-1) was dissolved in THF (100 ml) and cooled to -30 °C under Ar atmosphere. Butyllithium solution (2.5 M) (40.12 mL, 100 mmol, 1.2 eq) was added dropwise, and the reaction mixture was stirred at the same temperature for 30 min. The reaction mixture was cooled to -78 °. A solution of 4,4,5,5- tetramethyl-2-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) methyl]-1,3,2-dioxaborolane (24.63 g, 91.93 mmol, 1.1 eq, CAS 78782-17-9) in THF (20 ml) was added dropwise. After stirring for 30 min, a solution of tert-butyl 2-oxo-7-azaspiro[3.5]nonane-7-carboxylate (20 g, 83.57 mmol, 1 eq, CAS 203661-69-2) in THF (30 ml) was added dropwise at -78 °C. The reaction mixture was allowed to slowly warm up to RT and stirred overnight. The mixture was cooled to 0 °C, and aq. NH ₄ Cl (30 mL) was added dropwise. After additional stirring for 1 h, the resulting mixture was filtered and the solvent was concentrated in vacuo. H2O (100 mL) was added to the residue, and the aqueous layer was extracted with EtOAc (250 mL). The organic phase was washed with brine (250 mL), dried with anhydrous Na ₂ SO ₄ and concentrated in vacuo. The crude product was purified by column chromatography (Interchim, 330 g SiO2, hexane/MTBE (0-15-100%), flow rate = 100 ml/min, 5-9 CV) to afford tert-butyl 2-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)methylene]-7-azaspiro[3.5]nonane-7-carboxylate (20.4 g, 56.15 mmol, 63% yield) as white solid. MS (ESI): m/z = 308.2 [M-C ₄ H ₈ +H] ⁺ . C.9 1-bromo-3-dimethylphosphoryl-5-(trifluoromethyl)benzene To a solution of methylphosphonoylmethane (2.22 g, 28.5 mmol, CAS 150765-29-0), 1-bromo- 3-iodo-5-(trifluoromethyl)benzene (5 g, 14.3 mmol, CAS 481075-59-6), 9,9-dimethyl-4,5- bis(diphenylphosphino)xanthene (206 mg, 0.36 mmol, CAS 161265-03-8) and triethylamine (2.98 mL, 21.4 mmol) in 1,4-dioxane (50 mL) was added tris(dibenzylideneacetone)dipalladium (0) (130. mg, 0.14 mmol, CAS 51364-51-3). The reaction mixture was stirred at 25 °C under argon for 48 h. The reaction mixture was concentrated in vacuo. The residue was partitioned between ethyl acetate and water. The organic layer was washed with brine. The extract was dried over sodium sulfate and concantrated in vacuo. The crude product was purified by flash chromatography to afford the title compound (1.9 g, 6.31 mmol, 42% yield) as an orange solid. MS (ESI): m/z = 301.0 [M+H] ⁺ . C.17 3-bromo-5-[1-(trifluoromethyl)cyclopropyl]-4H-1,2,4-triazole To a solution of 3-[1-(trifluoromethyl)cyclopropyl]-1H-1,2,4-triazole (5.07 g, 27 mmol, 1 eq) in DMF (25 mL) was added NBS (10.65 g, 59.82 mmol, 2.2 eq). The mixture was stirred at 60 °C for 15 h. The reaction mixture was poured into EtOAc and washed with water, NaCl sat. The organic layer was dried over Na ₂ SO ₄ and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 40g, 0% to 20% EtOAc in heptane) to afford 5-bromo-3-[1- (trifluoromethyl)cyclopropyl]-1H-1,2,4-triazole (3.08 g, 42% yield) as white solid MS: (ESI): m/z = 255.9 [{79Br}M+H] ⁺ , 257.9 [{81Br}M+H] ⁺ . Step 1: (NE)-N-(dimethylaminomethylene)-1-(trifluoromethyl)cycloprop anecarboxamide 1-(trifluoromethyl)cyclopropanecarboxamide (5 g, 32 mmol, 1 eq, CAS 1628184-67-7) was dissolved in N,N-dimethylformamide dimethyl acetal (27.24 g, 228 mmol, 7 eq). The mixture was stirred at room temperature for 6 h. The reaction mixture was poured into EtOAc and washed with water, NaCl sat. The organic layer was dried over Na ₂ SO ₄ and concentrated in vacuo to afford (NE)-N-(dimethylaminomethylene)-1- (trifluoromethyl)cyclopropanecarboxamide (6.5 g, 90% yield) as yellow amorphous oil. MS (ESI): m/z = 209.1 [M+H] ⁺ . Step 2: 3-[1-(trifluoromethyl)cyclopropyl]-1H-1,2,4-triazole To a ice cooled solution of (NE)-N-(dimethylaminomethylene)-1- (trifluoromethyl)cyclopropanecarboxamide (6.5 g, 28 mmol, 1 eq) in acetic acid (18 mL) was added hydrazine;hydrate (1.55 g, 30.9 mmol, 1.1 eq). The mixture was stirred at 50 °C for 2 h. The reaction mixture concentrated in vacuo and dissolved in EtOAc. NaOH 1 N was added (pH 7-8). The mixture was washed with water, NaCl sat. The organic layer was dried over Na ₂ SO ₄ and concentrated in vacuo to afford 3-[1-(trifluoromethyl)cyclopropyl]-1H-1,2,4-triazole (5.07 g, 96% yield) as yellow solid. MS (ESI): m/z = 178.1 [M+H] ⁺ . C.72 1-bromo-4-dimethylphosphoryl-2-(trifluoromethyl)benzene To a solution of methylphosphonoylmethane (1.85 g, 23.7 mmol, CAS 7211-39-4), 1-bromo-4- iodo-2-(trifluoromethyl)benzene (8.3 g, 23.7 mmol, CAS 364-11-4), 9,9-dimethyl-4,5- bis(diphenylphosphino)xanthene (137 mg, 0.24 mmol, CAS 161265-03-8) and triethylamine (3.86 mL, 27.7 mmol) in 1,4-dioxane (80 mL) was added tris(dibenzylideneacetone)dipalladium (0) (108 mg, 0.12 mmol, CAS 51364-51-3). The mixture was stirred at RT under Ar for 24 h. The reaction mixture was filtered through celite, the filtrate was concentrated in vacuo. The residue was purified by FC (eluting with petroleum ether/MtBE with MtBE from 0-100%, further with MtBE/methanol with methanol from 0-25%) to afford 1-bromo-4- dimethylphosphoryl-2-(trifluoromethyl)benzene (50 mg, 0.170 mmol, 18.5% yield) as white semisolid. MS (ESI): m/z = 301.0 [{79Br}M+H] ⁺ , 303.0 [{81Br}M+H] ⁺ . C.115 2-bromo-3-methoxy-5-(trifluoromethyl)pyrazine To a mixture of 3-methoxy-5-(trifluoromethyl)pyrazin-2-amine (1.6 g, 8.28 mmol, CAS 1823377-58-7) and CuBr (1.42 g, 9.94 mmol) in ACN (15 mL) was added a solution of tert- butyl nitrite (1.28 g, 12.4 mmol) in ACN (5 mL) at 25 °C. The reaction mixture was stirred at 70 °C under N2 atmosphere for 12 h. The reaction mixture was filtered, the filtrate was concentrated in vacuo at room temperature. The residue was purified by column chromatography (ethyl acetate:petroleum ether 0-10%) and concentrated in vacuo at room temperature to give the title compound (800 mg, 3.11 mmol, 38% yield) as a colorless oil. MS (ESI): m/z = 256.9 [M+H] ⁺ . NOTE:The product was volatile. C.122 3-bromo-5-[1-(trifluoromethyl)cyclopropyl]-1H-pyrazole To a solution of 5-[1-(trifluoromethyl)cyclopropyl]-1H-pyrazol-3-amine (2.3 g, 12 mmol, CAS 1001354-47-7) in ACN (40 mL) was added dropwise a solution of isopentyl nitrite (1.55 g, 13.2 mmol) in ACN (5 mL) at 0 °C. The reaction mixture was stirred at 0 °C for 1 h. CuBr2 (1.61 g, 7.22 mmol) was added to the mixture at 0 °C and the resulting mixture was stirred at 20 °C for 12 h. The reaction mixture was concentrated in vacuo. The residue was purified by reversed- phase HPLC (water(0.1%FA)-ACN]). The purified solution was lyophilized to afford the title compound (740 mg, 2.9 mmol, 24.1% yield) as a light green solid. MS (ESI): m/z = 257.2 [M+H] ⁺ . C.124 2-chloro-5-[1-(trifluoromethyl)cyclopropyl]pyrazine To a solution of 2-chloro-5-[1-(trifluoromethyl)vinyl]pyrazine (1.6 g, 7.67 mmol) in THF (60 mL) was added diphenyl(methyl)sulfonium tetrafluoroborate (2.87 g, 9.97 mmol, CAS 10504- 60-6). The suspension was stirred at 0 °C for 0.5 h. A solution of NaHMDS (12.3 mL, 12.3 mmol, 1 M in THF) was added dropwise. The reaction mixture was heated at 25 °C for 1 h. Water (50 mL) was added to the reaction mixture and the aqueous phase was extracted with EtOAc (40 mL) twice. The organic layers were combined, washed with brine, dried over Na2SO4 and concantrated in vacuo. Purification by FC (SiO2; PE/EtOAc) gave the title compound (1.5 g, 63% yield) as a yellow oil. ¹ H NMR (400 MHz, chloroform-d) δ = 8.53 (s, 1H), 8.43 (d, J = 1.2 Hz, 1H), 1.48 - 1.42 (m, 2H), 1.36 ppm (br s, 2H). Step 1: 2-chloro-5-[1-(trifluoromethyl)vinyl]pyrazine To a solution of 4,4,6-trimethyl-2-[1-(trifluoromethyl)vinyl]-1,3,2-dioxabori nane (3.44 g, 15.5 mmol, CAS 1011460-68-6) and 2-bromo-5-chloropyrazine (3 g, 15.5 mmol), potassium carbonate (4.29 g, 31 mmol) in 1,4-dioxane (60 mL) and water (6 mL) was added 1,1'- bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (1266 mg, 1.55 mmol, CAS 95464-05-4). The mixture was stirred at 80 °C under N ₂ atmosphere for 12 h, filtered and concentrated in vacuo. Purification by FC (SiO ₂ ; PE) gave the title compound (1.6 g, 49 % yield) as a yellow solid. MS (ESI): m/z =209.3 [M+H] ⁺ C.125 3-bromo-6-[1-(trifluoromethyl)cyclopropyl]pyridazine To a solution of 3-bromo-6-[1-(trifluoromethyl)vinyl]pyridazine (340 mg, 1.34 mmol) in THF (10 mL) was added diphenyl(methyl)sulfonium tetrafluoroborate (503 mg, 1.75 mmol, CAS 10504-60-6). The suspension was stirred at 0 °C for 0.5 h. A solution of NaHMDS (2.15 mL, 2.15 mmol, 1 M in THF) was added dropwise. The reaction mixture was stirred at 25 °C for 1 h. The mixture was quenched with 6 mL methanol. The reaction mixture was partitioned between EtOAc (20 mL) and water (40 mL). The organic phase was concentrated in vacuo. Purification by prep-HPLC gave the title compound (280 mg, 78 % yield) as a white solid. MS (ESI): m/z = 267.3 [M+H] ⁺ . Step 1: 3-bromo-6-[1-(trifluoromethyl)vinyl]pyridazine To a solution of 4,4,6-trimethyl-2-[1-(trifluoromethyl)vinyl]-1,3,2-dioxabori nane (560 mg, 2.52 mmol, CAS 1011460-68-6) and 3,6-dibromopyridazine (500 mg, 2.1 mmol), potassium carbonate (581 mg, 4.2 mmol) in 1,4-dioxane (10 mL) and water (2 mL) was added 1,1'- bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (172 mg, 0.210 mmol, CAS 95464-05-4). The mixture was stirred at 80 °C under N2 atmosphere for 3 h. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (200 mL x 3). The combined organic phase was washed with brine, dried over Na ₂ SO ₄ and concentrated in vacuo. Purification by FC (SiO2; PE) gave the title compound (300 mg, 56 % yield) as a white crystalline solid. MS (ESI): m/z = 253.3 [M+H] ⁺ . C.128 4,5-dibromo-2-(2,2,2-trifluoroethyl)triazole To a solution of 4,5-dibromo-2H-triazole (5 g, 22 mmol, CAS 22300-52-3) in ACN (50 mL) was added cesium carbonate (7.18 g, 22 mmol).2,2,2-trifluoroethyl trifluoromethanesulfonate (5.12 g, 22.0 mmol, CAS 6226-25-1) was added dropwise at 0 °C. The reaction mixture was stirred for 16 h at RT. The reaction mixture was poured into water. EtOAc was added and the aqueous layer was extracted with EtOAc. The organic layer was washed with water and brine, dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The crude product was purified by column chromatography (silica gel, PE/EtOAc 0-7%). The fractions containing the pure product were combined and concentrated in vacuo to give 4,5-dibromo-2-(2,2,2-trifluoroethyl)triazole (5.3 g, 17.2 mmol, 77% yield) as yellow oil. ¹ H NMR (400 MHz, chloroform-d) δ = 4.95 (q, J = 7.9 Hz, 2H). C.145 2-[[5-bromo-3-(trifluoromethyl)pyrazolo[3,4-c]pyridin-1-yl]m ethoxy]ethyl-trimethyl-silane A mixture of 2-[(5-bromo-3-iodo-pyrazolo[3,4-c]pyridin-1-yl)methoxy]ethyl -trimethyl-silane (5.6 g, 12 mmol, 1 eq, CAS 2097610-93-8), copper(I) iodide (11.74 g, 61 mmol, 5 eq), potassium fluoride (3.58 g, 61 mmol, 5 eq), and trifluoromethyltrimethylsilane (8.77 g, 61 mmol, 5 eq) in NMP (113 mL) was stirred for 18 h at 100 °C. The reaction mixture was quenched by the addition of 1 L of water and filtered from inorganic precipitate. The filtrate was extracted with ethyl acetate and the organic phase was washed with water, saturated NaCl solution, dried over Na ₂ SO4 and concentrated in vacuo. The crude material was purified by FC to give 2-[[5-bromo-3-(trifluoromethyl)pyrazolo[3,4-c]pyridin-1-yl]m ethoxy]ethyl-trimethyl- silane (1.4 g, 3.5 mmol, 28% yield) as a light yellow viscous oil. MS (ESI): m/z = 396.0 [M+H] ⁺ . FC conditions: Interchim, 120 SiO ₂ , hexane/ethyl acetate (0-22%), flow rate = 80ml/min. C.149 1-(4-bromophenyl)sulfonyl-3-(trifluoromethyl)azetidine To a solution of 4-bromobenzenesulfonyl chloride (1.33 g, 5.2 mmol, 1.3 eq) and 3- (trifluoromethyl)azetidine (500 mg, 4 mmol, 1 eq, CAS 1221349-18-3) in DMF (5 mL) was added DIEA (3.46 mL, 20 mmol, 5 eq) at 25 °C. The mixture was shaken for 2 h at 100 °C. The crude material was purified by flash column (PE to PE:EtOAc=3:1;UV ) and concentrated in vacuo to give 1-(4-bromophenyl)sulfonyl-3-(trifluoromethyl)azetidine (980 mg, 2.85 mmol, 71% yield) as white solid. MS (ESI): m/z = 344.0 [{79Br}M+H] ⁺ , 346.0 [{81Br}M+H] ⁺ . C.157 4-chloro-2-methylsulfonyl-1-(trifluoromethyl)benzene To a solution of 4-chloro-2-methylsulfanyl-1-(trifluoromethyl)benzene (1.95 g, 8.6 mmol, 1 eq, CAS 1428234-60-9) in 1,2-dichloroethane (20 mL) - ACN (20 mL) - water (40 mL), sodium periodate (3.68 g, 17.21 mmol, 2 eq) and ruthenium(III) chloride hydrate (19.4 mg, 0.09 mmol, 0.01 eq) were added at 0 °C. The mixture was stirred at 25°C for 12h. The reaction mixture was diluted with water (40 ml), extracted with 50 mL DCM, 2 x 50 mL EtOAc. The combined organic layers were washed with 75 mL brine, dried over Na ₂ SO ₄ and filtered. The filtrate was concentrated in vacuo. The residue was purified by column chromatography (SiO ₂ , petroleum ether:ethyl acetate=.3:1 ) to give 4-chloro-2-methylsulfonyl-1-(trifluoromethyl)benzene (1.8 g, 6.96 mmol, 72% yield) as a white soild.1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.32 (d, J=1.96 Hz, 1 H) 7.87 (d, J=8.44 Hz, 1 H) 7.76 (dd, J=8.44, 1.22 Hz, 1 H) 3.22 (s, 3 H). C.158 7-chloro-3-(trifluoromethyl)imidazo[1,2-a]pyrimidine In pre-cooled (liquid N ₂ ) lithium;7-chloroimidazo[1,2-a]pyrimidine-3-carboxylate (2.5 g, 12.28 mmol, 1 eq, CAS 2839138-71-3) in an autoclave hydrogen fluoride (7.45 mL, 368.53 mmol, 30 eq) was placed. Then tetrafluoro-λ4-sulfane (2.65 g, 24.57 mmol, 2 eq, CAS 7783-60-0) was pressurized into the vessel. Then the reaction mixture was stirred at 65 °C for 72 h. The reaction mixture was carefully diluted with sat. K ₂ CO ₃ (150 ml). The aqueous layer was extracted with MTBE. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo and purified by FC to afford 7-chloro-3-(trifluoromethyl)imidazo[1,2- a]pyrimidine (500 mg, 2.25 mmol, 16.3% yield as white solid. MS (ESI): m/z = 222.0 [M+H] ⁺ . FC conditions: 1) Interchim, 12 g SiO2, chloroform/acetonitrile (0-10%), flow rate = 80 ml/min, 6,2-9,6 CV; 2) Interchim, 40 g SiO2, hexane/isopropanol (5-100%), flow rate = 40 ml/min, RV =7,8-31,1 CV. C.160 2-bromo-5-[3-(trifluoromethyl)azetidin-1-yl]pyrazine To a solution of 3- (trifluoromethyl)azetidine;hydrochloride (500 mg, 3.08 mmol, 1 eq, CAS 1221272-90-7) and DIEA (1.55 g, 15.3 mmol, 5 eq) in DMF (10 mL) was added 2,5-dibromopyrazine (951 mg, 4 mmol, 1.3 eq). The resulting solution was stirred at 100 °C for 2 h. The reaction mixture was poured into sat. NaCl. The mixture was extracted with EtOAc. The organic phase was dried over anhydrous Na ₂ SO ₄ and concentrated in vacuo. The crude product was purified by column chromatography(SiO2, petroleum ether/EtOAc) and concentrated in vacuo to give 2-bromo-5-[3- (trifluoromethyl)azetidin-1-yl]pyrazine (500 mg, 1.77 mmol, 44% yield) as yellow solid. MS (ESI): m/z = 281.9 [M+H] ⁺ . C.171 3-bromo-1-(2,2,2-trifluoroethyl)-1,2,4-triazole To a solution of 3-bromo-1H-1,2,4-triazole (8 g, 54 mmol, 1 eq, CAS 7343-33-1) in THF (80 mL) was added NaH (3.89 g, 97 mmol, 1.8 eq) at 0 °C. After 0.5 h, 2,2,2-trifluoroethyl trifluoromethanesulfonate (25.1 g, 108.14 mmol, 2 eq, CAS 6226-25-1) was added. The mixture was stirred at 20 °C for 12 h. The reaction mixture was poured into water and extracted with EtOAc. The organic layer was washed with brine, dried over Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by pre-HPLC(Welch Ultimate XB-SiOH 250*70*10um, hexane-EtOH) and was concentrated in vacuo to give 3-bromo-1-(2,2,2-trifluoroethyl)-1,2,4- triazole (6 g, 26.09 mmol, 48% yield) as brown oil. MS (ESI): m/z = 229.9 [M+H] ⁺ . C.195 2-chloro-4-[1-(trifluoromethyl)cyclopropyl]pyrimidine To a solution of 2-chloro-4-[1-(trifluoromethyl)vinyl]pyrimidine (1 g, 4.79 mmol, 1 eq) in THF (5 mL) and was added diphenyl(methyl)sulfonium tetrafluoroborate (2.07 g, 7.19 mmol, 1.5 eq, CAS 10504-60-6) and NaHMDS (7.67 mL, 7.67 mmol, 1.6 eq) at 20 °C. The mixture was stirred at 20 °C for 12 h under N2. The reaction mixture was poured into H2O, extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo to afford 2-chloro-4-[1-(trifluoromethyl)cyclopropyl]pyrimidine (1 g, 4.49 mmol, 93% yield) as red oil. MS (ESI): m/z = 233.0 [M+H] ⁺ . Step 1: 2-chloro-4-[1-(trifluoromethyl)vinyl]pyrimidine To a solution of 4-bromo-2-chloropyrimidine (2 g, 10.34 mmol, 1 eq, CAS 885702-34-1) 4,4,6- trimethyl-2-[1-(trifluoromethyl)vinyl]-1,3,2-dioxaborinane (2.29 g, 10.34 mmol, 1 eq, CAS 1011460-68-6) and K2CO3 (2.85 g, 20.68 mmol, 2 eq) in 1,4-dioxane (40 mL) and water (4 mL) was added 1,1'-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (844 mg, 1.03 mmol, 0.1 eq, CAS 95464-05-4). The mixture was stirred at 25 °C for 12 h. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (SiO2, Eluent of 0-3% ethyl acetate/petroleum ether,Rf=0.6) and concentrated in vacuo to give 2-chloro-4-[1-(trifluoromethyl)vinyl]pyrimidine (1.36 g, 6.54 mmol, 62% yield) as yellow oil. MS (ESI): m/z = 208.9 [M+H] ⁺ .