PROCESS AND INTERMEDIATES FOR PREPARING A JAK INHIBITOR FIELD The present invention is related to processes for preparing ruxolitinib, salts thereof, and related synthetic intermediate compounds and salts thereof. Ruxolitinib and salts thereof are useful as inhibitors of the Janus Kinase family of protein tyrosine kinases (JAKs) for treatment of inflammatory diseases, myeloproliferative disorders, and other diseases. BACKGROUND Protein kinases (PKs) are a group of enzymes that regulate diverse, important biological processes including cell growth, survival and differentiation, organ formation and morphogenesis, neovascularization, tissue repair and regeneration, among others. Protein kinases exert their physiological functions through catalyzing the phosphorylation of proteins (or substrates) and thereby modulating the cellular activities of the substrates in various biological contexts. In addition to the functions in normal tissues/organs, many protein kinases also play more specialized roles in a host of human diseases including cancer. A subset of protein kinases (also referred to as oncogenic protein kinases), when dysregulated, can cause tumor formation and growth, and further contribute to tumor maintenance and progression (Blume-Jensen P. et al., Nature 2001, 411(6835):355-365). Thus far, oncogenic protein kinases represent one of the largest and most attractive groups of protein targets for cancer intervention and drug development. Protein kinases can be categorized as receptor type and non-receptor type. Receptor tyrosine kinases (RTKs) have an extracellular portion, a transmembrane domain, and an intracellular portion, while non-receptor tyrosine kinases are entirely intracellular. The Janus kinase family of protein tyrosine kinases (JAKs) belong to the non-receptor type of tyrosine kinases and include family members: JAK1 (also known as Janus kinase-1), JAK2 (also known as Janus kinase-2), JAK3 (also known as Janus kinase, leukocyte; JAKL; L-JAK and Janus kinase-3) and TYK2 (also known as protein-tyrosine kinase 2). The pathway involving JAKs and Signal Transducers and Activators of Transcription (STATs) is engaged in the signaling of a wide range of cytokines. Cytokines are low-molecular weight polypeptides or glycoproteins that stimulate biological responses in virtually all cell types. Generally, cytokine receptors do not have intrinsic tyrosine kinase activity, and thus require receptor-associated kinases to propagate a phosphorylation cascade. JAKs fulfill this function. Cytokines bind to their receptors, causing receptor dimerization, and this enables JAKs to phosphorylate each other as well as specific tyrosine motifs within the cytokine receptors. STATs that recognize these phosphotyrosine motifs are recruited to the receptor, and are then themselves activated by a JAK-dependent tyrosine phosphorylation event. Upon activation, STATs dissociate from the receptors, dimerize, and translocate to the nucleus to bind to specific DNA sites and alter transcription (Scott, M. J., C. J. Godshall, et al. (2002). "Jaks, STATs, Cytokines, and Sepsis." Clin Diagn Lab Immunol 9(6): 1153-9). The JAK family plays a role in the cytokine-dependent regulation of proliferation and function of cells involved in immune response. The JAK/STAT pathway, and in particular all four members of the JAK family, are believed to play a role in the pathogenesis of the asthmatic response, chronic obstructive pulmonary disease, bronchitis, and other related inflammatory diseases of the lower respiratory tract. Moreover, multiple cytokines that signal through JAK kinases have been linked to inflammatory diseases or conditions of the upper respiratory tract such as those affecting the nose and sinuses (e.g., rhinitis, sinusitis) whether classically allergic reactions or not. The JAK/STAT pathway has also been implicated to play a role in inflammatory diseases/conditions of the eye including, but not limited to, iritis, uveitis, scleritis, conjunctivitis, as well as chronic allergic responses. Therefore, inhibition of JAK kinases may have a beneficial role in the therapeutic treatment of these diseases. Blocking signal transduction at the level of the JAK kinases holds promise for developing treatments for human cancers. Inhibition of the JAK kinases is also envisioned to have therapeutic benefits in patients suffering from skin immune disorders such as psoriasis, and skin sensitization. Accordingly, inhibitors of Janus kinases or related kinases are widely sought and several publications report effective classes of compounds. For example, JAK inhibitor ruxolitinib, ((R)-3-(4-(7H- pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentyl propanenitrile) is reported in U.S. Pat. App. Pub. Nos.2007/0135461, 2010/190981, and 2008/0312259; and their disclosures are incorporated herein by reference. In view of the growing demand for compounds for the treatment of disorders related to the inhibition of kinases such as Janus kinases, new and more efficient routes to ruxolitinib, salts thereof, and intermediates related thereto, are needed. The processes and compounds described herein help meet these and other needs. SUMMARY The present disclosure provides, inter alia, processes of preparing ruxolitinib, salts thereof, and related synthetic intermediate compounds and salts of the intermediates. Accordingly, the present disclosure provides processes of preparing ruxolitinib, or a salt thereof, comprising reacting a compound of formula 3: or a salt thereof, with a reagent selected from (i) a salt of formula 2a and (ii) a compound of formula 2b: wherein X- is a counter anion. The present disclosure further provides processes of preparing ruxolitinib, or a salt thereof, comprising reacting a salt of formula 2c: with a L-(+)-tartrate salt of a compound of formula 3: to form the ruxolitinib, or the salt thereof. The present disclosure also provides processes of preparing ruxolitinib, or a salt thereof, comprising reacting a salt of formula 2c: with a salt of formula 3a: to form the ruxolitinib, or the salt thereof. The present disclosure further provides processes of preparing ruxolitinib, or a salt thereof, comprising: (a) reacting a salt of formula 2d: with a base to form a salt of formula 2c: ; and (b) reacting the salt of formula 2c with a salt of formula 3a: to form the ruxolitinib, or the salt thereof. In some embodiments of the previous processes, the salt of formula 2d is prepared by a process comprising: (a) reacting a compound of formula 2P: with MeMgBr in the presence of a Grignard catalyst to form a compound of formula 1aP: (b) deprotecting the compound of formula 1aP to form a compound of formula 1a: or a salt thereof; and (c) reacting the compound of formula 1a, or the salt thereof, with a Vilsmeier reagent formed from dimethylformamide and a chlorinating agent to form the salt of formula 2d; wherein P ¹ is an amino protecting group. In some embodiments of the previous processes, the salt of formula 2d is prepared by a process comprising: (a) reacting a compound of formula 22P: with MeMgBr in the presence of a Grignard catalyst to form a compound of formula 23P: ; (b) reducing the compound of formula 23P to form a compound of formula 1a: or a salt thereof; and (c) reacting the compound of formula 1a, or the salt thereof, with a Vilsmeier reagent formed from dimethylformamide and a chlorinating agent to form the salt of formula 2d; wherein P ² is an amino protecting group. In some embodiments of the previous processes, the salt of formula 3a is prepared by a process comprising: (a) reacting a compound of formula 6a: with hydrazine to form a compound of formula 7a: and (b) reacting the compound of formula 6a with L-tartaric acid to form the salt of formula 3a. The present disclosure further provides a compound or a salt selected from: (a) , or a salt thereof; or (b) ; or (c) or (d) or a salt thereof; or (e) , or a salt thereof; or (f) , or a salt thereof; or (g) , or a salt thereof; or (h) , or a salt thereof; or (i) , wherein X- is a counter anion other than Cl-; or (j) ; or (k) ; or (l) ; or (m) ; or (n) ; or (o) . The present disclosure still further provides a crystalline form of a salt of formula 2d: 2d selected from Form I and Form II. The present disclosure also provides a crystalline form of a salt of formula 3a: 3a. DESCRIPTION OF DRAWINGS FIG.1 is an X-ray powder diffraction (XRPD) pattern of Compound 2d Form I. FIG.2 is a differential scanning calorimetry (DSC) thermogram of Compound 2d Form I. FIG.3 is a thermogravimetric analysis (TGA) thermogram of Compound 2d Form I. FIG.4 is an XRPD pattern of Compound 2d Form II. FIG.5 is a DSC thermogram of Compound 2d Form II. FIG.6 is a TGA thermogram of Compound 2d Form II. FIG.7 is an XRPD pattern of Compound 2 hexafluorophosphate. FIG.8 is a DSC thermogram of Compound 2 hexafluorophosphate. FIG.9 is a TGA thermogram Compound 2 hexafluorophosphate. FIG.10A is a single X-ray crystal structure of Compound 3a showing one molecule. FIG.10B is a single X-ray crystal structure of Compound 3a showing repeating units of Compound 3a. FIG.11 is an XRPD pattern of Compound 3a. FIG.12 a DSC thermogram of Compound 3a. FIG.13 a TGA thermogram of Compound 3a. The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims. DETAILED DESCRIPTION The present disclosure provides a process of preparing ruxolitinib, also known as (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)- 3- cyclopentylpropanenitrile, and intermediates thereof as well as salts and crystalline forms of ruxolitinib and intermediates. Ruxolitinib (also known as INCB018424) is sold as the phosphate salt under the trade names JAKAFI and JAKAVI, and has the following structure: Compound 1. (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)- 3- cyclopentylpropanenitrile is also referred to as Compound 1 in this disclosure. The compound and various processes of preparing the compound are disclosed in U.S. Pat. App. Pub. Nos.2007/0135461, 2010/190981, and 2008/0312259, which are hereby incorporated herein by reference. The present disclosure provides a process of preparing ruxolitinib, or a salt thereof, comprising: reacting a compound of formula 3: or a salt thereof, with a reagent selected from (i) a salt of formula 2a, or a salt thereof, and (ii) a compound of formula 2b: wherein X- is a counter anion. The present disclosure provides a process of preparing ruxolitinib, or a salt thereof, comprising: reacting a compound of formula 3: or a salt thereof, with a reagent selected from (i) a salt of formula 2a, and (ii) a compound of formula 2b: wherein X- is a counter anion. In some embodiments, the reagent is the salt of formula 2a. In some embodiments, the reagent is the compound of formula 2b. In some embodiments, the reagent is the salt of the salt of formula 2a, wherein X- is Cl-. In some embodiments, the reagent is the hydrochloric acid salt of the salt of formula 2a, wherein X- is Cl-. In some embodiments, the compound of formula 3, or the salt thereof, is a chiral salt of the compound of formula 3. The chiral salt can be prepared by reacting the compound of formula 3 with an optically active form of an acid selected from mandelic acid, 2-chloromandelic acid, camphorsulfonic acid, tartaric acid, lactic acid, malic acid, 3-bromocamphor-8- sulfonic acid, 3-bromocamphor-10-sulfonic acid, 10-camphorsulfonic acid, dibenzoyl tartaric acid, di-p-toluoyltartaric acid, 2-amino-7,7-dimethylbicyclop[2,2,1]heptan-1- methylene sulfonic acid, and 2-acrylamide-7,7-dimethylbicyclo[2,2,1] heptan-1- methylene sulfonic acid. In some embodiments, the chiral salt is the L-(+)-tartrate salt of the compound of formula 3. In some embodiments, the compound of formula 3, or the salt thereof, has formula 3a: In some embodiments, from about 1 to about 1.5 molar equivalent of the reagent ((i) a salt of formula 2a, or (ii) a compound of formula 2b) is utilized relative to the compound of formula 3, or salt thereof. For example, about 1.25 molar equivalent of the reagent is utilized relative to the compound of formula 3, or salt thereof. For example, about 1 molar equivalent of the reagent is utilized relative to the compound of formula 3, or salt thereof. In some embodiments, the reacting of the reagent ((i) a salt of formula 2a, or (ii) a compound of formula 2b) with the compound of formula 3, or the salt thereof, is carried out in a solvent component S1. The solvent component S1 can comprise a polar protic solvent or a polar aprotic solvent. In some embodiments, solvent component S1 comprises water. In some embodiments, the solvent component S1 comprises an alcohol. In some embodiments, the solvent component S1 comprises formula C _1-6 alkyl-OH. In some embodiments, the solvent component S1 is ethanol. In some embodiments, the solvent component S1 comprises dimethylformamide. In some embodiments, the solvent component S1 comprises water, an alcohol or a combination thereof. In some embodiments, the reagent is the salt of formula 2a. X- can be selected from Cl-, Br-, I-, BF ₄ -, PF ₆ -, AsF ₆ -, SbF ₆ -, and ClO ₄ -. In some embodiments, X- is selected from Cl-, BF4-, PF ₆ -, AsF ₆ -, SbF ₆ -, and ClO ₄ -. In some embodiments, X- is BF4-. In some embodiments, X- is PF ₆ -. In some embodiments, X- is AsF ₆ -. In some embodiments, X- is SbF ₆ -. In some embodiments, X- is ClO ₄ -. In some embodiments, X- is Cl-. In some embodiments, the reagent is the compound of formula 2b. The compound of formula 2b can be prepared by a process comprising reacting the salt of formula 2a with a base B1. In some embodiments, the reacting of the salt of formula 2a with the base B1 is conducted in a solvent component S2 comprising water. In some embodiments, the base B1 is a strong base. In some embodiments, the base B1 is a hydroxide. In some embodiments, the base B1 is an alkali metal hydroxide. In some embodiments, the base B1 is sodium hydroxide. In some embodiments, from about 10 to about 15 molar equivalents of the base B1 is utilized relative to the salt of formula 2a or salt thereof. In some embodiments, from about 12 molar equivalents of the base B1 is utilized relative to the salt of formula 2a or salt thereof. In some embodiments, the reacting of the salt of formula 2a with the base B1 is conducted at a temperature of from about -10 °C to about 60 °C. In some embodiments, temperature is from about 0 °C to room temperature. In some embodiments, temperature is from about 40 °C to about 60 °C. In some embodiments, the temperature is from 0 °C to room temperature and then heated to from about 40 °C to about 60 °C. In some embodiments, the salt of formula 2a or the compound of formula 2b can be prepared by a process comprising: reacting the compound of formula 1a: 1a, or a salt thereof, with a Vilsmeier reagent formed from dimethylformamide. In some embodiments, the salt of formula 2a or the compound of formula 2b can be prepared by a process comprising: reacting the compound of formula 5a: 5a, or a salt thereof, with a Vilsmeier reagent formed from dimethylformamide. In some embodiments, the compound of formula 5a is a salt. For example, the compound of formula 5ais the sodium salt. In some embodiments, the reacting with the Vilsmeier reagent produces a compound of formula 2c: In some embodiments, after the reacting with a Vilsmeier reagent, the compound of formula 2c is reacted with a salt of formula M ⁺ X-, wherein M ⁺ is a counter cation. In some embodiments, the Vilsmeier reagent is prepared by a process comprising reacting dimethylformamide with a chlorinating agent. In some embodiments, the chlorinating agent is selected from oxalyl chloride, phosphorus oxychloride, triphosgene, thionyl chloride, sulfuryl chloride, and phosphorus pentachloride. In some embodiments, the chlorinating agent is selected from oxalyl chloride, phosphorus oxychloride, and triphosgene. In some embodiments, the chlorinating agent is oxalyl chloride. In some embodiments, the chlorinating agent is phosphorus oxychloride. In some embodiments, the chlorinating agent is triphosgene. In some embodiments, from about 1 to about 5 molar equivalents of the chlorinating agent are utilized relative to the compound of formula 1a or 5a, or the salt thereof. In some embodiments, from about 1 to about 4 molar equivalents of the chlorinating agent are utilized relative to the compound of formula 1a or 5a, or the salt thereof. In some embodiments, from about 1 to about 3 molar equivalents of the chlorinating agent are utilized relative to the compound of formula 1a or 5a, or the salt thereof. In some embodiments, about 1 molar equivalent of the chlorinating agent is utilized relative to the compound of formula 1a or 5a, or the salt thereof. In some embodiments, about 2 molar equivalents of the chlorinating agent are utilized relative to the compound of formula 1a or 5a, or the salt thereof. In some embodiments, about 3 molar equivalents of the chlorinating agent are utilized relative to the compound of formula 1a or 5a, or the salt thereof. In some embodiments, about 4 molar equivalents of the chlorinating agent are utilized relative to the compound of formula 1a or 5a, or the salt thereof. In some embodiments, about 5 molar equivalents of the chlorinating agent are utilized relative to the compound of formula 1a or 5a, or the salt thereof. In some embodiments, from about 10 to about 25 molar equivalents of dimethylformamide are utilized relative to the compound of formula 1a or 5a, or the salt thereof. In some embodiments, from about 10 to about 20 molar equivalents of dimethylformamide are utilized relative to the compound of formula 1a or 5a, or the salt thereof. In some embodiments, from about 10 to about 15 molar equivalents of dimethylformamide are utilized relative to the compound of formula 1a or 5a, or the salt thereof. In some embodiments, from about 11 to about 14 molar equivalents of dimethylformamide are utilized relative to the compound of formula 1a or 5a, or the salt thereof. In some embodiments, from about 11 to about 13 molar equivalents of dimethylformamide are utilized relative to the compound of formula 1a. In some embodiments, the preparation of the Vilsmeier reagent is carried out in a solvent component S3. In some embodiments, the solvent component S3 comprises an organic solvent. In some embodiments, the solvent component S3 comprises a polar aprotic solvent. In some embodiments, the solvent component S3 comprises acetonitrile, dimethyformamide, or a combination thereof. In some embodiments, the Vilsmeier reagent is prepared at a temperature between from about -10 °C to about 60 °C. In some embodiments, the Vilsmeier reagent is prepared at a temperature between from about -10 °C to about 30 °C. For example, the Vilsmeier reagent is prepared at a temperature between from about -10 °C to about room temperature. For example, the temperature is about 0 °C to about room temperature. In some embodiments, the Vilsmeier reagent is prepared at a temperature between from about room temperature to about 60 °C. In some embodiments, the Vilsmeier reagent is prepared at a temperature between from about 30 °C to about 70 °C, about 40 °C to about 70 °C, about 30 °C to about 60 °C, or about 40 °C to about 60 °C. In some embodiments, the Vilsmeier reagent is prepared at a temperature between from about 75 °C to about 80 °C, 80 °C to 90 °C, or 85 °C to 90 °C. In some embodiments, the reacting of the compound of formula 1a or 5a, or the salt thereof, with the Vilsmeier reagent is carried out at a temperature of from about 40 °C to about 100 °C. In some embodiments, the reacting of the compound of formula 1a or 5a, or the salt thereof, with the Vilsmeier reagent is carried out at a temperature of from about 70 °C to about 100 °C. In some embodiments, the reacting of the compound of formula 1a or 5a, or the salt thereof, with the Vilsmeier reagent is carried out at a temperature of from about 40 °C to about 60 °C. In some embodiments, the product of the reacting with the Vilsmeier reagent has formula 2d: 2d. In some embodiments, the salt of formula 2a can be formed by a process comprising: reacting the salt of formula 2c: 2c, with a salt of formula M ⁺ X-, wherein: M ⁺ is a counter cation; and X- is a counter anion other than Cl-. In some embodiments, M ⁺ is an alkali metal counter cation. For example, M ⁺ is Li ⁺ , Na ⁺ or K ⁺ . In some embodiments, M ⁺ is Na ⁺ . In some embodiments, X- is selected from Br-, I-, BF4-, PF ₆ -, AsF ₆ -, SbF ₆ -, and ClO ₄ -. For example, X- is selected from BF ₄ - , PF ₆ -, AsF ₆ -, SbF ₆ -, and ClO ₄ -. In some embodiments, X- is BF ₄ -. In some embodiments, X- is PF ₆ -. In some embodiments, X- is AsF ₆ -. In some embodiments, X- is SbF ₆ -. In some embodiments, X- is ClO ₄ -. In some embodiments, the salt of formula 2c can be produced by a process comprising: reacting a salt of formula 2d: with a base. In some embodiments, the compound of formula 2b is prepared by a process comprising reacting a salt of formula 2d with a base B2. In some embodiments, (i) the reacting of the salt of formula 2d with a base B2 and (ii) the reacting of the salt of formula 2d with the compound of formula 3 are conducted in a single pot. In some embodiments, the reacting of the salt of formula 2d with a base B2 is conducted in a solvent component comprising water. In some embodiments, the base B2 is a strong base. In some embodiments, the base B2 is a hydroxide base. In some embodiments, the base B2 is an alkali metal hydroxide. For example, the base B2 is sodium hydroxide. In some embodiments, the reacting of the salt of formula 2d with a base B2 is conducted at a temperature of from about -10 °C to about 15 °C. In some embodiments, the compound of formula 1a, or the salt thereof, is the hydrochloride salt. In some embodiments, the compound of formula 1a, or the salt thereof, can be prepared by a process comprising: deprotecting a compound of formula 1aP: wherein P ¹ is an amino protecting group. In some embodiments, P ¹ is selected from (R ¹ )3Si, wherein R ¹ is C _1-6 alkyl. In some embodiments, R ¹ is methyl, ethyl, propyl, isopropyl, butyl or t-butyl. In some embodiments, P ¹ is t-butyldimethylsilyl. In some embodiments, the deprotecting is carried out by reacting the compound of formula 1aP with a base B3. In some embodiments, the base B3 is a hydroxide base. For example, the base B3 is ammonium hydroxide. In some embodiments, the deprotecting is carried out in a solvent component S4. In some embodiments, the solvent component S4 comprises a polar protic solvent. In some embodiments, the solvent component S4 comprises an alcohol. In some embodiments, the solvent component S4 comprises formula C _1-6 alkyl-OH. For example, the solvent component S4 comprises methanol. In some embodiments, the compound of formula 1aP can be prepared by a process comprising: reacting a compound of formula 2P: with MeMgBr in the presence of a Grignard catalyst, wherein P ¹ is an amino protecting group. In some embodiments, the catalyst is an iron catalyst. In some embodiments, the iron catalyst is iron(III) acetylacetonate. In some embodiments, from about 1 to about 2 molar equivalents of MeMgCl are utilized relative to the compound of formula 2P. In some embodiments, from about 1% to about 10% molar equivalents of the catalyst are utilized relative to the compound of formula 2P. In some embodiments, the reacting of the compound formula 2P with MeMgCl is carried out in a solvent component S5. In some embodiments, the solvent component S5 comprises a di-C _1-6 alkyl ether or a 4-10 membered heterocycloalkyl ether. For example, the solvent component S5 comprises a tetrahydrofuran. In some embodiments, the reacting of the compound formula 2P with MeMgCl is carried out at a temperature of from about -10 °C to about 30 °C. In some embodiments, the compound of formula 2P can be prepared by a process comprising: protecting a compound of formula 12a: 12a to form the compound of formula 2P. In some embodiments, the protecting comprises reacting the compound of formula 12a with an alkali metal hydride and P ¹ -Y, wherein Y is halo. In some embodiments, P ¹ -Y is (R ¹ )3Si-Y, wherein Y is halo and R ¹ is C _1-6 alkyl. In some embodiments, P ¹ is (R ¹ ) ₃ Si, wherein R ¹ is C _1-6 alkyl. In some embodiments, R ¹ is methyl, ethyl, propyl, isopropyl, butyl or t-butyl. In some embodiments, P ¹ is t- butyldimethylsilyl. In some embodiments, the alkali metal hydride is sodium hydride. In some embodiments, from about 1 to about 2 molar equivalents of the alkali metal hydride is utilized relative to the compound of formula 12a. In some embodiments, from about 1 to about 2 molar equivalents of P ¹ -Y is utilized relative to the compound of formula 12a. In some embodiments, the reacting of the compound of formula 12a with the alkali metal hydride and P ¹ -Y is carried out at a temperature of about -10 °C to about 20 °C. In some embodiments, the reacting of the compound of formula 12a with the alkali metal hydride and P ¹ -Y is carried out in a solvent component S6, wherein the solvent component S6 comprises an organic solvent. In some embodiments, the solvent component S6 comprises a di-C _1-6 alkyl ether or a 4-10 membered heterocycloalkyl ether. In some embodiments, the solvent component S6 comprises a tetrahydrofuran. In some embodiments, the compound of formula 1a, or the salt thereof, can be prepared by a process comprising: reducing a compound of formula 23P: wherein P ² is an amino protecting group. In some embodiments, the reducing of the compound of formula 23P is accomplished by a process comprising reacting the compound of formula 23P with hydrogen gas in the presence of a catalyst. For example, the catalyst is Pd ⁰ on carbon. In some embodiments, the amount of the catalyst relative to the compound of formula 23P is about 5% to about 15% by weight In some embodiments the reacting of the compound of formula 23P with hydrogen and the catalyst is carried out at a temperature of about 40 °C to about 70 °C. In some embodiments, the reacting of the compound of formula 23P with hydrogen and the catalyst is carried out at a temperature of about 50 °C to about 60 °C. In some embodiments, the reacting of the compound of formula 23P with hydrogen and the catalyst is carried out at a temperature of about 50 °C to about 55 °C. In some embodiments, the reacting of the compound of formula 23aP with hydrogen and the catalyst is carried out in a solvent component S7. In some embodiments, the solvent component S7 comprises a polar protic solvent. In some embodiments, the solvent component S7 comprises an alcohol. In some embodiments, the solvent component S7 comprises formula C _1-6 alkyl-OH. For example, the solvent component S7 comprises methanol. In some embodiments, the compound of formula 23P can be prepared by a process comprising: reacting a compound of formula 22P: with MeMgBr in the presence of a Grignard catalyst, wherein P ² is an amino protecting group. In some embodiments, the catalyst is an iron catalyst. For example, the iron catalyst is iron(III) acetylacetonate. In some embodiments, from about 1 to about 2 molar equivalents of MeMgCl is utilized relative to the compound of formula 22P. In some embodiments, from about 1% to about 10% molar equivalents of the catalyst are utilized relative to the compound of formula 22P. In some embodiments, the reacting of the compound formula 22P with MeMgCl is carried out in a solvent component S8. In some embodiments, the solvent component S8 comprises a di-C _1-6 alkyl ether or a 4-10 membered heterocycloalkyl ether. For example, the solvent component S8 comprises a tetrahydrofuran. In some embodiments, the reacting of the compound formula 2P with MeMgCl is carried out at a temperature of from about -10 °C to about 30 °C. In some embodiments, the compound of formula 22P can be prepared by a process comprising: protecting a compound of formula 22a: to form the compound of formula 22P. In some embodiments, the protecting comprise reacting the compound of formula 22a with an alkali metal hydride and P ² -Y, wherein Y is halo. In some embodiments, P ² is (R ¹ )3Si, wherein R ¹ is C _1-6 alkyl. In some embodiments, R ¹ is methyl, ethyl, propyl, isopropyl, butyl or t-butyl. In some embodiments, P ² is t- butyldimethylsilyl. In some embodiments, the alkali metal hydride is sodium hydride. In some embodiments, from about 1 to about 2 molar equivalents of the alkali metal hydride is utilized relative to the compound of formula 22a. In some embodiments, from about 1 to about 2 molar equivalents of P ² -Y is utilized relative to the compound of formula 22a. In some embodiments, the reacting of the compound of formula 22a with the alkali metal hydride and P ² -Y is carried out at a temperature of about -10 °C to about 20 °C. In some embodiments, the reacting of the compound of formula 22a with the alkali metal hydride and P ² -Y is carried out in a solvent component S9, wherein the solvent component S9 comprises an organic solvent. In some embodiments, the solvent component S9 comprises a di-C _1-6 alkyl ether or a 4- 10 membered heterocycloalkyl ether. For example, the solvent component S9 comprises a tetrahydrofuran. In some embodiments, the compound of formula 1a, or the salt thereof, can be prepared by a process comprising: reacting a compound of formula 18a: with an acid Al to form the compound of formula la.

In some embodiments, the acid Al is a strong acid. For example, the acid Al is hydrochloric acid. In some embodiments, the reacting of the compound of formula 18a with the acid Al is carried out in a solvent component S10, wherein the solvent component S10 comprises a polar protic solvent. In some embodiments, the solvent component S10 comprises an alcohol. In some embodiments, the solvent component S10 comprises formula Ci-6 alkyl-OH. For example, the solvent component S10 comprises isopropyl alcohol.

In some embodiments, the compound of formula 18a, or a salt thereof, can be prepared by a process comprising: reacting a compound of formula 17a: with formamidine acetate and triethyl orthoformate to form the compound of formula 17a.

In some embodiments, from about 10 to about 15 molar equivalents of formamidine acetate is utilized relative to the compound of formula 17a. In some embodiments, about 10, about 11, about 12, about 13, about 14, or about 15 molar equivalents of formamidine acetate is utilized relative to the compound of formula 17a. In some embodiments, about 12 molar equivalents of formamidine acetate is utilized relative to the compound of formula 17a. In some embodiments, from about 6 to about 10 molar equivalents of triethyl orthoformate is utilized relative to the compound of formula 17a. In some embodiments, about 6, about 7, about 8, about 9, or about 10 molar equivalents of tri ethyl orthoformate is utilized relative to the compound of formula 17a. For example, about 8 molar equivalents of triethyl orthoformate is utilized relative to the compound of formula 17a. In some embodiments, the reacting of the compound of formula 17a with formamidine acetate and tri ethyl orthoformate is carried out at a temperature of about 100 °C to about 150 °C. For example, the temperature can be about 110 °C to about 120 °C. In some embodiments, the reacting of the compound of formula 17a with formamidine acetate and tri ethyl orthoformate is carried out in a solvent component SI 1, wherein the solvent component S11 comprises a polar protic solvent. In some embodiments, the solvent component S11 comprises an alcohol. In some embodiments, the solvent component S11 comprises formula C _1-6 alkyl-OH. For example, the solvent component S11 comprises 1-butanol. In some embodiments, the compound of formula 17a, or a salt thereof, can be prepared by a process comprising: reacting a compound of formula 20a: with a compound of formula 21a: 21a to form the compound of formula 17a. In some embodiments, from about 0.4 to about 1 molar equivalents of the compound of formula 21a is utilized relative to the compound of formula 20a. In some embodiments, the reacting of the compound of formula 20a with the compound of formula 21a is carried out at room temperature. In some embodiments, the reacting of the compound of formula 20a with the compound of formula 21a is carried out in a solvent component S12, wherein the solvent component S12 comprises a polar aprotic solvent. For example, the solvent component S12 comprises dimethylformamide. In some embodiments, the compound of formula 20a, or a salt thereof, can be prepared by a process comprising: reacting a compound of formula 19a: with bromo-1,1-dimethoxyethane and a base B4 to form the compound of formula 20a. In some embodiments, the base B4 is an alkali metal carbonate. For example, the base B4 is cesium carbonate. In some embodiments, from about 1 to about 2 molar equivalents of the base B4 is utilized relative to the compound of formula 19a. In some embodiments, from about 1 to about 2 molar equivalents of bromo-1,1- dimethoxyethane is utilized relative to the compound of formula 19a. In some embodiments, the reacting of the compound of formula 19a with bromo-1,1- dimethoxyethane is carried out at a temperature of about 70 °C to about 100 °C. In some embodiments, the reacting of the compound of formula 19a with bromo-1,1- dimethoxyethane is carried out in a solvent component S13, wherein the solvent component S13 comprises a polar aprotic solvent. In some embodiments, the solvent component S13 comprises dimethylformamide. In some embodiments, the compound of formula 17a, or a salt thereof, can prepared by a process comprising: reacting a compound of formula 16a: with ethyl acetate and a base B5 to form the compound of formula 17a. In some embodiments, the base B5 is an alkali metal alkoxide. For example, the base B5 is potassium tert-butoxide. In some embodiments, from about 1 to about 3 molar equivalents of the base B5 is utilized relative to the compound of formula 16a. In some embodiments, from about 1 to about 2 molar equivalents of ethyl acetate is utilized relative to the compound of formula 16a. In some embodiments, about 2 molar equivalents of the base B5 is utilized relative to the compound of formula 16a. In some embodiments, the reacting of the compound of formula 17a with ethyl acetate and a base B5 is carried out at room temperature. In some embodiments, the reacting of the compound of formula 17a with ethyl acetate and a base B5 is carried out in a solvent component S14, wherein the solvent component S14 comprises an organic solvent. In some embodiments, the solvent component S14 comprises a di-C _1-6 alkyl ether or a 4-10 membered heterocycloalkyl ether. For example, the solvent component S14 comprises a tetrahydrofuran. In some embodiments, the compound of formula 5a, or the salt thereof, can be prepared by a process comprising: hydrolyzing a compound of formula 27a: in water in the presence of a base B6. In some embodiments, the base B6 is an alkali metal hydroxide. For example, the base B6 is sodium hydroxide. In some embodiments, from about 1 to about 2 molar equivalents of the base B6 is utilized relative to the compound of formula 27a. In some embodiments, about 1.5 molar equivalents of the base B6 is utilized relative to the compound of formula 27a. In some embodiments, the hydrolyzing of the compound of formula 27a is carried out at room temperature. In some embodiments, the hydrolyzing of the compound of formula 27a is carried out in a solvent component S15, wherein the solvent component S15 comprises an organic solvent. For example, the solvent component S15 comprises tetrahydrofuran, acetone, or a combination thereof. In some embodiments, the compound of formula 5a, or the salt thereof, is the sodium salt of the compound of formula 5a. In some embodiments, the compound of formula 5a, or the salt thereof, is the compound of formula 5a. In some embodiments, the compound of formula 5a can be prepared by a process comprising reacting the sodium salt of the compound of formula 5a with a strong acid A2. For example, the strong acid A2 is hydrochloric acid. In some embodiments, (a) the reacting of the sodium salt of compound of formula 5a with a strong acid A2 and (b) the hydrolyzing of the sodium salt of the compound of formula 27a is carried out in a single pot. In some embodiments, the compound of formula 27a can be prepared by a process comprising: reacting a compound of formula 26P: with a strong acid A3, wherein P ¹ is an amino protecting group. In some embodiments, P ¹ is p-toluenesulfonyl. For example, A3 is hydrochloric acid. In some embodiments, the reacting of the compound of formula 26P with a strong acid A3 is carried out at room temperature. In some embodiments, the reacting of the compound of formula 26P with a strong acid A3 is carried out in a solvent component S16. In some embodiments, the solvent component S16 comprises formula C _1-6 alkyl-OH. In some embodiments, the solvent component S16 comprises ethanol. In some embodiments, the compound of formula 26P can be prepared by a process comprising: reacting a compound of formula 25P: with alkali metal alkoxide B8 to form the compound of formula 26P, wherein P ¹ is an amino protecting group. In some embodiments, about 0.1 molar equivalents of alkali metal alkoxide B8 is utilized relative to the compound of formula 25P. In some embodiments, the reacting of the compound of formula 25P with alkali metal alkoxide B8 is carried out at room temperature. In some embodiments, the reacting of the compound of formula 25P with alkali metal alkoxide B8 is carried out in a solvent component S17, wherein the solvent component S17 comprises a polar protic solvent. For example, the alkali metal alkoxide B8 is sodium ethoxide. In some embodiments, the solvent component S17 comprises an alcohol. In some embodiments, the solvent component S17 comprises formula C _1-6 alkyl-OH. For example, the solvent component S17 comprises ethanol. In some embodiments, the compound of formula 27a can be prepared by a process comprising: reacting a compound of formula 25P: with an alkali metal alkoxide B9 to form the compound of formula 27a. In some embodiments, from about 1 to about 2 molar equivalents of alkali metal alkoxide B9 is utilized relative to the compound of formula 25P. In some embodiments, about 1 molar equivalent of alkali metal alkoxide B9 is utilized relative to the compound of formula 25P. In some embodiments, the reacting of the compound of formula 25P with an alkali metal alkoxide B9 is carried out at a temperature of about 50 °C to about 80 °C. In some embodiments, the reacting of the compound of formula 25P with an alkali metal alkoxide B9 is carried out in a solvent component S18, wherein the solvent component S18 comprises formula C _1-6 alkyl-OH. For example, the solvent component S18 comprises ethanol. In some embodiments, the compound of formula 25P can be prepared by a process comprising: reacting a compound of formula 2P: with diethyl malonate and a base B10, wherein P ¹ is an amino protecting group. In some embodiments, the base B10 is an alkali metal carbonate. For example, the base B10 is cesium carbonate. In some embodiments, the reacting of the compound of formula 2P with a base B10 is carried out at a temperature of about 40 °C to about 70 °C. In some embodiments, the reacting of the compound of formula 2P with a base B10 is carried out in a solvent component S19, wherein the solvent component S19 comprises a polar aprotic solvent. For example, the solvent component S19 comprises dimethylformamide. In some embodiments, the compound of formula 2P can be prepared by a process comprising protecting a compound of formula 12a to form the compound of formula 2P. In some embodiments, the protecting comprise reacting the compound of formula 12a with a base B11 and P ¹ -Y, wherein Y is halo. For example, P ¹ is p- toluenesulfonyl. In some embodiments, the base B11 is an alkali metal hydroxide. For example, the base B11 is sodium hydroxide. In some embodiments, the protecting comprise reacting the compound of formula 12a with a base B11 is carried out in a solvent component S20, wherein the solvent component S20 comprises a polar aprotic solvent. For example, the solvent component S20 comprises acetone. In some embodiments, the compound of formula 12a can be prepared by a process comprising reacting a compound of formula 11a: or a salt thereof, with a strong acid A4. In some embodiments, the strong acid A4 is hydrochloric acid. In some embodiments, the reacting of the compound of formula 11a, or a salt thereof, with a strong acid A4 is carried out in a solvent component S21, wherein the solvent component S21 comprises a polar aprotic solvent. In some embodiments, the solvent component S21 comprises a di-C _1-6 alkyl ether or a 4-10 membered heterocycloalkyl ether. For example, the solvent component S21 comprises tetrahydrofuran. In some embodiments, the reacting of the compound of formula 11a, or a salt thereof, with a strong acid A4 is carried out at the refluxing temperature of tetrahydrofuran. In some embodiments, the compound of formula 11a can be prepared by a process comprising reacting a compound of formula 10a: or a salt thereof, with (methoxymethyl)triphenylphosphonium chloride and a base B12. In some embodiments, the base B12 is an alkali metal alkoxide. For example, the base B12 is potassium t-butoxide. In some embodiments, the reacting of the compound of formula 11a, or a salt thereof, with (methoxymethyl)triphenylphosphonium chloride and a base B12 is carried out at a temperature of about 10 °C to about 30 °C. In some embodiments, the reacting of the compound of formula 11a, or a salt thereof, with (methoxymethyl)triphenylphosphonium chloride and a base B12 is carried out in a solvent component S22, wherein the solvent component S22 comprises a polar aprotic solvent. In some embodiments, the solvent component S22 comprises a di-C _1-6 alkyl ether or a 4-10 membered heterocycloalkyl ether. For example, the solvent component S22 comprises tetrahydrofuran. In some embodiments, the compound of formula 10a, or a salt thereof, can be prepared by a process comprising reacting a compound of formula 9a: with ammonia. In some embodiments, the reacting of the compound of formula 9a with ammonia is carried out at a temperature of about 40 °C to about 70 °C. In some embodiments, the reacting of the compound of formula 9a with ammonia is carried out in a solvent component S23, wherein the solvent component S23 comprises organic solvent. For example, the solvent component S23 comprises toluene. In some embodiments, the compound of formula 9a can be prepared by a process comprising reacting a compound of formula 8a: with a Vilsmeier reagent formed from dimethylformamide. In some embodiments, the Vilsmeier reagent is prepared by a process comprising reacting dimethylformamide with a chlorinating agent. In some embodiments, the chlorinating agent is selected from oxalyl chloride, phosphorus oxychloride, triphosgene, thionyl chloride, sulfuryl chloride, and phosphorus pentachloride. For example, the chlorinating agent is phosphorus oxychloride. In some embodiments, about 4 to about 6 molar equivalents (e.g., 5 molar equivalents) of the chlorinating agent is utilized relative to a compound of formula 8a. In some embodiments, about 1 to about 3 molar equivalents (e.g., 2 molar equivalents) of the dimethylformamide is utilized relative to a compound of formula 8a. In some embodiments, the reacting dimethylformamide with a chlorinating agent is prepared at a temperature from about -10 °C to about 20 °C (e.g., about 0 °C to about 10 °C). In some embodiments, the reacting of a compound of formula 8a with a Vilsmeier reagent is carried out at a temperature from about 80 °C to about 130 °C (e.g., about 90 °C to about 120 °C, or about 95 °C to about 115 °C). In some embodiments, the compound of formula 12a can be prepared by a process comprising reacting a compound of formula 15a: with a chlorinating agent. In some embodiments, the chlorinating agent is selected from oxalyl chloride, phosphorus oxychloride, triphosgene, thionyl chloride, sulfuryl chloride, and phosphorus pentachloride. In some embodiments, the chlorinating agent is phosphorus oxychloride. In some embodiments, the reacting of the compound of formula 15a with a chlorinating agent is carried out at a temperature of about 50 °C to about 100 °C. In some embodiments, the reacting of the compound of formula 15a with ammonia is carried out in a solvent component S24, wherein the solvent component S24 comprises an organic solvent. For example, the solvent component S24 comprises toluene. In some embodiments, the compound of formula 15a can be prepared by a process comprising: (i) reacting a compound of formula 14a: 14a with formamidine acetate and an alkali metal hydroxide to generate a compound of formula 14aa: ; and (ii) reacting the compound of formula 14aa with a strong acid A4. In some embodiments, the alkali metal hydroxide is sodium ethoxide. In some embodiments, the reacting of the compound of formula 14a with formamidine acetate and an alkali metal hydroxide is carried out at a temperature of about 50 °C to about 100 °C. In some embodiments, the reacting of the compound of formula 14a with formamidine acetate and an alkali metal hydroxide is carried out in a solvent component S25, wherein the solvent component S25 comprises a polar protic solvent. In some embodiments, the solvent component S25 comprises an alcohol. In some embodiments, the solvent component S25 comprises formula C _1-6 alkyl-OH. For example, the solvent component S25 comprises ethanol. For example, the strong acid A4 is hydrochloric acid. In some embodiments, the compound of formula 14a can be prepared by a process comprising reacting a compound of formula 13a: with bromoacetaldehyde diethyl acetal and sodium tert-amyloxide. In some embodiments, the reacting of the compound of formula 13a with bromoacetaldehyde diethyl acetal and sodium tert-amyloxide is carried out at a temperature of about 80 °C to about 100 °C. In some embodiments, the reacting of the compound of formula 13a with bromoacetaldehyde diethyl acetal and sodium tert- amyloxide is carried out in a solvent component S26, wherein the solvent component S26 comprises a polar aprotic solvent. In some embodiments, the solvent component S26 comprises dimethylsulfoxide. In some embodiments, the compound of formula 3a, or the salt thereof, is the L-tartrate salt of the compound of formula 3. In some embodiments, the L-tartrate salt of formula 3 can be prepared by a process comprising: reacting Compound 7a: with L-tartaric acid. In some embodiments, about 1 molar equivalent of L-tartaric acid is utilized relative to the compound of formula 7a. In some embodiments, the reacting of the compound of formula 7a with L-tartaric acid is carried out in a solvent component S27. In some embodiments, the solvent component S27 comprises water and organic solvent. In some embodiments, the solvent component S27 comprises about 1:1 (v) of water to organic solvent. In some embodiments, the solvent component S27 comprises a polar aprotic solvent. For example, the solvent component S27 comprises acetonitrile. In some embodiments, the reacting of the compound of formula 7a with L-tartaric acid is carried out at a temperature of from about 20 °C to about 30 °C. In some embodiments, the reacting of the compound of formula 7a and L-tartaric acid further comprises seeding with the salt of formula 3a. In some embodiments, the compound of formula 7a can be prepared by a process comprising reacting the compound of formula 6a: with hydrazine. In some embodiments, from about 2 to about 3 equivalents of hydrazine is utilized relative to Compound 6a. In some embodiments, the hydrazine is hydrazine hydrate. In some embodiments, the reacting of the compound of formula 6a with hydrazine is carried out a temperature of from about -10 °C to about 30 °C. In some embodiments, the salt of ruxolitinib is ruxolitinib phosphate. In some embodiments, the ruxolitinib phosphate can be prepared by a process comprising reacting ruxolitinib with phosphoric acid. In some embodiments, from about 1 to about 2 molar equivalents of phosphoric acid is utilized relative to ruxolitinib. In some embodiments, the reacting of ruxolitinib with phosphoric acid is carried out a temperature of about 20 °C to about 50 °C. In some embodiments, the phosphoric acid is an aqueous solution of phosphoric acid. In some embodiments, the ruxolitinib phosphate is purified by a process comprising: (i) adding a first solvent component to ruxolitinib phosphate to generate a first solution; (ii) concentrating the first solution to generate a second solution; (iii) adding a second solvent component to the second solution to generate a third solution; (iv) adding a third solvent component to the third solution to generate a fourth solution; (v) concentrating the fourth solution to generate a fifth solution; and (vi) isolating ruxolitinib phosphate from the fifth solution. In some embodiments, the first solvent component comprises C _1-6 alkyl-OH. In some embodiments, the first solvent component comprises methanol. In some embodiments, the first solution is heated to a temperature between about 30 °C to about 80 °C. In some embodiments, the second solvent component comprises C _1-6 alkyl-OH. For example, the second solvent component comprises isopropyl alcohol. In some embodiments, the temperature of the second solution is between about 30 °C to about 80 °C. In some embodiments, the third solvent component comprises a non- polar solvent. In some embodiments, the third solvent comprises a C _1-8 alkane. For example, the third solvent comprises n-heptane. In some embodiments, the temperature of the third solution is between about 30 °C to about 80 °C. In some embodiments, the fifth solution is cooled to about 20 °C to about 30 °C. The present disclosure also provides a process of preparing ruxolitinib phosphate, comprising: (a) reacting a compound of formula 1a, or a salt thereof: with a Vilsmeier reagent formed from dimethylformamide to generate a compound of formula 2c: 2c; (b) reacting the compound of formula 2c with a L-tartrate salt of a compound of formula 3: to provide ruxolitinib; and (c) reacting ruxolitinib with phosphoric acid to generate ruxolitinib phosphate. In some embodiments, the compound of formula 1a or a salt thereof can be prepared by a process comprising: (a) reacting a compound of formula 12a: with t-butyldimethylsilyl chloride to generate a compound of formula 12b: ; (b) reacting the compound of formula 12b with MeMgBr in the presence of a Grignard catalyst to generate a compound of formula 12c: and (c) deprotecting the compound of formula 12c to generate a compound of formula 1a or a salt thereof. In some embodiments, the compound of formula 1a or a salt thereof can be prepared by a process comprising: (a) reacting a compound of formula 22a: with t-butyldimethylsilyl chloride and MeMgBr in the presence of a Grignard catalyst to generate a compound of formula 23a : (b) reacting the compound of formula 23a with hydrogen and palladium on carbon to generate a compound of formula 1a or a salt thereof. In some embodiments, the process of preparing ruxolitinib, or a salt thereof, comprises reacting a salt of formula 2a: with a L-(+)-tartrate salt of a compound of formula 3: to form the ruxolitinib, or the salt thereof, wherein X- is a counterion. In some embodiments, the process of preparing ruxolitinib, or a salt thereof, comprises reacting a salt of formula 2c: with a L-(+)-tartrate salt of a compound of formula 3: to form the ruxolitinib, or the salt thereof. In some embodiments, the process of preparing ruxolitinib, or a salt thereof, comprises reacting a salt of formula 2a: with a salt of formula 3a: to form the ruxolitinib, or the salt thereof, wherein X- is a counterion. In some embodiments, the process of preparing ruxolitinib, or a salt thereof, comprises reacting a salt of formula 2c: with a salt of formula 3a: to form the ruxolitinib, or the salt thereof. In some embodiments, the process of preparing ruxolitinib, or a salt thereof, comprises: (a) reacting a salt of formula 2d: with a base to form a salt of formula 2c: ; and (b) reacting the salt of formula 2c with a salt of formula 3a: to form the ruxolitinib, or the salt thereof. In some embodiments of the previous processes, the salt of formula 2d is prepared by a process comprising: (a) reacting a compound of formula 2P: with MeMgBr in the presence of a Grignard catalyst to form a compound of formula 1aP: (b) deprotecting the compound of formula 1aP to form a compound of formula 1a: or a salt thereof; and (c) reacting the compound of formula 1a, or the salt thereof, with a Vilsmeier reagent formed from dimethylformamide and a chlorinating agent to form the salt of formula 2d; wherein P ¹ is an amino protecting group. In some embodiments, P ¹ is trimethylsilyl. In other embodiments, the salt of formula 2d is prepared by a process comprising: (a) reacting a compound of formula 22P: with MeMgBr in the presence of a Grignard catalyst to form a compound of formula 23P: (b) reducing the compound of formula 23P to form a compound of formula 1a: or a salt thereof; and (c) reacting the compound of formula 1a, or the salt thereof, with a Vilsmeier reagent formed from dimethylformamide and a chlorinating agent to form the salt of formula 2d; wherein P ² is an amino protecting group. In some embodiments, P ¹ is t- butyldimethylsilyl. In some embodiments of the previous processes, the salt of formula 3a is prepared by a process comprising: (a) reacting a compound of formula 6a: 6a with hydrazine to form a compound of formula 7a: ; and (b) reacting the compound of formula 6a with L-tartaric acid to form the salt of formula 3a. The present disclosure also provides a compound which is or a salt thereof. In some embodiments, the compound or a salt thereof is selected from: , and . Provided herein is a compound which is or a salt thereof. Provided herein is a compound which is or a salt thereof. Provided herein is a compound which is or a salt thereof. Provided herein is a compound which is or a salt thereof. Provided herein is a compound which is or a salt thereof. Provided herein is a compound which is a salt of formula 2a: wherein X- is a counter anion, and X- is other than Cl-. In some embodiments, the compound is selected from: (Compound 2 chloride hydrochloride), (Compound 2 perchlorate), (Compound 2 tetrafluoroborate), (Compound 2 hexfluorophosphate), (Compound 2 hexafluoroarsenate), and (Compound 2 hexafluoroantimonate). In some embodiments, the present disclosure provides a salt of formula 2d: 41 In some embodiments, the salt of formula 2d can be isolated as a crystalline solid. In some embodiments, provided herein are crystalline forms of the salt of formula 2d. In some embodiments, the crystalline form of the salt of formula 2d is Form I. In some embodiments, Form I has an XRPD pattern substantially as shown in Figure 1. Form I can have a DSC thermogram substantially as depicted in Figure 2. In some embodiments, Form I has a TGA thermogram substantially as depicted in Figure 3. In some embodiments, Form I has at least one XRPD peak, in terms of 2-theta (± 0.2 degrees), selected from 7.4, 12.5, 13.1, 14.1, 14.6, 15.0, 15.9, 17.7, 18.5, 19.0, 20.5, 20.8, 22.2, 23.0, 24.3, 26.3, and 27.9 degrees. In some embodiments, Form I has at least two XRPD peaks, in terms of 2-theta (± 0.2 degrees), selected from 7.4, 12.5, 13.1, 14.1, 14.6, 15.0, 15.9, 17.7, 18.5, 19.0, 20.5, 20.8, 22.2, 23.0, 24.3, 26.3, and 27.9 degrees. In some embodiments, Form I has at least three XRPD peaks, in terms of 2-theta (± 0.2 degrees), selected from 7.4, 12.5, 13.1, 14.1, 14.6, 15.0, 15.9, 17.7, 18.5, 19.0, 20.5, 20.8, 22.2, 23.0, 24.3, 26.3, and 27.9 degrees. In some embodiments, Form I has at least four XRPD peaks, in terms of 2-theta (± 0.2 degrees), selected from 7.4, 12.5, 13.1, 14.1, 14.6, 15.0, 15.9, 17.7, 18.5, 19.0, 20.5, 20.8, 22.2, 23.0, 24.3, 26.3, and 27.9 degrees. In some embodiments, Form I has characteristic XRPD peaks, in terms of 2-theta (± 0.2 degrees), at 7.4, 12.5, 13.1, 14.1, 14.6, 15.0, 15.9, 17.7, 18.5, 19.0, 20.5, 20.8, 22.2, 23.0, 24.3, 26.3, and 27.9 degrees. In some embodiments, Form I has an endothermic peak with an onset temperature (± 3 °C) at 56 °C and a maximum at 101 °C in a DSC thermogram. In some embodiments, the crystalline form of salt of formula 2d is Form II. In some embodiments, Form II has an XRPD pattern as substantially shown in Figure 4. In some embodiments, Form II has a DSC thermogram substantially as depicted in Figure 5. In some embodiments, Form II a TGA thermogram substantially as depicted in Figure 6. In some embodiments, Form II has at least one XRPD peak, in terms of 2- theta (± 0.2 degrees), selected from 7.3, 11.5, 11.9, 13.3, 15.5, 15.8, 16.1, 17.4, 19.1, 19.4, 19.6, 21.4, 22.0, 22.6, 23.2, 24.9, 25.5, 26.7, and 29.1 degrees. In some embodiments, Form II has at least two XRPD peaks, in terms of 2-theta (± 0.2 degrees), selected from 7.3, 11.5, 11.9, 13.3, 15.5, 15.8, 16.1, 17.4, 19.1, 19.4, 19.6, 21.4, 22.0, 22.6, 23.2, 24.9, 25.5, 26.7, and 29.1 degrees. In some embodiments, Form II has at least three XRPD peaks, in terms of 2-theta (± 0.2 degrees), selected from 7.3, 11.5, 11.9, 13.3, 15.5, 15.8, 16.1, 17.4, 19.1, 19.4, 19.6, 21.4, 22.0, 22.6, 23.2, 24.9, 25.5, 26.7, and 29.1 degrees. In some embodiments, Form II has at least four XRPD peaks, in terms of 2-theta (± 0.2 degrees), selected from 7.3, 11.5, 11.9, 13.3, 15.5, 15.8, 16.1, 17.4, 19.1, 19.4, 19.6, 21.4, 22.0, 22.6, 23.2, 24.9, 25.5, 26.7, and 29.1 degrees. In some embodiments, Form II has characteristic XRPD peaks, in terms of 2-theta (± 0.2 degrees), at 7.3, 11.5, 11.9, 13.3, 15.5, 15.8, 16.1, 17.4, 19.1, 19.4, 19.6, 21.4, 22.0, 22.6, 23.2, 24.9, 25.5, 26.7, and 29.1 degrees. In some embodiments, Form II has an endothermic peak with an onset temperature (± 3 °C) at 47 °C and a maximum at 99 °C in a DSC thermogram. In some embodiments, provided herein is a crystalline form of compound 2 hexfluorophosphate: (compound 2 hexfluorophosphate). In some embodiments, the crystalline form of compound 2 hexfluorophosphate has an XRPD pattern as substantially shown in Figure 7. In some embodiments, the crystalline form of Compound 2 hexfluorophosphate has a DSC thermogram substantially as depicted in Figure 8. In some embodiments, the crystalline form of compound 2 hexfluorophosphate has a TGA thermogram substantially as depicted in Figure 9. In some embodiments, the crystalline form of compound 2 hexfluorophosphate has at least one XRPD peak, in terms of 2-theta (± 0.2 degrees), selected from 10.8, 12.0, 13.9, 14.3, 15.2, 16.6, 17.0, 17.6, 18.1, 20.1, 20.4, 21.3, 21.5, 22.1, 24.2, 24.7, 25.0, and 26.3 degrees. In some embodiments, the crystalline form of Compound 2 hexfluorophosphate has at least two XRPD peaks in terms of 2 theta (± 0.2 degrees), selected from 10.8, 12.0, 13.9, 14.3, 15.2, 16.6, 17.0, 17.6, 18.1, 20.1, 20.4, 21.3, 21.5, 22.1, 24.2, 24.7, 25.0, and 26.3 degrees. In some embodiments, the crystalline form of Compound 2 hexfluorophosphate has at least three XRPD peaks, in terms of 2-theta (± 0.2 degrees), selected from 10.8, 12.0, 13.9, 14.3, 15.2, 16.6, 17.0, 17.6, 18.1, 20.1, 20.4, 21.3, 21.5, 22.1, 24.2, 24.7, 25.0, and 26.3 degrees. In some embodiments, the crystalline form of Compound 2 hexfluorophosphate has at least four XRPD peaks, in terms of 2-theta (± 0.2 degrees), selected from 10.8, 12.0, 13.9, 14.3, 15.2, 16.6, 17.0, 17.6, 18.1, 20.1, 20.4, 21.3, 21.5, 22.1, 24.2, 24.7, 25.0, and 26.3 degrees. In some embodiments, the crystalline form of Compound 2 hexfluorophosphate has characteristic XRPD peaks, in terms of 2-theta (± 0.2 degrees), at 10.8, 12.0, 13.9, 14.3, 15.2, 16.6, 17.0, 17.6, 18.1, 20.1, 20.4, 21.3, 21.5, 22.1, 24.2, 24.7, 25.0, and 26.3 degrees. In some embodiments, the crystalline form of compound 2 hexfluorophosphate has a first endothermic peak with an onset temperature (± 3 °C) at 232 °C and a maximum at 233 °C and a second endothermic peak with an onset temperature (± 3 °C) at 241 °C and a maximum at 242 °C in a DSC thermogram. In some embodiments, the crystalline form of the salt of formula 3a is characterized by single crystal x-ray diffraction having a monoclinic P21 space group and cell formula units (Z) of 4. In some embodiments, the monoclinic P21 space group has unit cell parameters: a is about 7.68 Å, b is about 7.60 Å, c is about 13.72 Å, and beta is about 96.94°. In some embodiments, the salt of formula 3a has a chiral purity of greater than 95%. In some embodiments, the salt of formula 3a has a chiral purity of greater than 97%. In some embodiments, the salt of formula 3a has a chiral purity of greater than 99%. In some embodiments, provided herein are processes of preparing ruxolitinib and its salts, e.g., phosphate salt. For example, ruxolitinib and its phosphate salt can be prepared according to one or more steps shown in Scheme 1. Scheme 1

The present disclosure further provides ruxolitinib, or a salt thereof, which is prepared according to a process provided herein.

The present disclosure further provides a salt of ruxolitinib, which is prepared according to a process provided herein.

The present disclosure further provides ruxolitinib, which is prepared according to a process provided herein. The present disclosure further provides ruxolitinib, or a pharmaceutically acceptable salt thereof, which is prepared according to a process provided herein.

The present disclosure further provides a pharmaceutically acceptable salt of ruxolitinib, which is prepared according to a process provided herein.

The present disclosure further provides ruxolitinib phosphate, which is prepared according to a process provided herein. At various places in the present specification, substituents of compounds of the invention are disclosed in groups or in ranges. It is specifically intended that the invention include each and every individual subcombination of the members of such groups and ranges. For example, the term “C _1-6 alkyl” is specifically intended to individually disclose methyl, ethyl, C ₃ alkyl, C ₄ alkyl, C ₅ alkyl, and C ₆ alkyl. It is further appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, can also be provided in combination in a single embodiment. Conversely, various features of the invention which are, for brevity, described in the context of a single embodiment, can also be provided separately or in any suitable subcombination. In some embodiments, the reagents or solvent components may be referred by by number (e.g., solvent component S1 or base B1). These numbers are present merely to further the antecedent basis for later dependent claim and therefore, in some embodiments, may be removed. For compounds of the invention in which a variable appears more than once, each variable can be a different moiety independently selected from the group defining the variable. For example, where a structure is described having two R groups that are simultaneously present on the same compound, the two R groups can represent different moieties independently selected from the group defined for R. In another example, when an optionally multiple substituent is designated in the form: then it is understood that substituent R can occur p number of times on the ring, and R can be a different moiety at each occurrence. It is understood that each R group may replace any hydrogen atom attached to a ring atom, including one or both of the (CH ₂ ) _n hydrogen atoms. Further, in the above example, should the variable Q be defined to include hydrogens, such as when Q is the to be CH ₂ , NH, etc., any floating substituent such as R in the above example, can replace a hydrogen of the Q variable as well as a hydrogen in any other non-variable component of the ring. As used herein, the term “alkyl”, employed alone or in combination with other terms, refers to a saturated hydrocarbon group that may be straight-chain or branched. In some embodiments, the alkyl group contains 1 to 12, 1 to 8, or 1 to 6 carbon atoms. Examples of alkyl moieties include, but are not limited to, chemical groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl; higher homologs such as 2-methyl-1-butyl, n-pentyl, 3-pentyl, n-hexyl, 1,2,2- trimethylpropyl, n-heptyl, n-octyl, and the like. In some embodiments, the alkyl moiety is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, or 2,4,4-trimethylpentyl. In some embodiments, the alkyl moiety is methyl. As used herein, the terms “halo” and “halogen”, employed alone or in combination with other terms, refer to fluoro, chloro, bromo, and iodo. As used herein, the term "4-10 membered heterocycloalkyl ether" refers to a non- aromatic ring or ring system, which optionally contain one or more alkenylene groups as part of the ring structure, which has at least one oxygen heteroatom ring member and 4- 10 ring members. Included within the term “heterocycloalkyl” are monocyclic 4-, 5-, 6- and 7-membered heterocycloalkyl groups. Examples of 4-10 membered heterocycloalkyl ether include tetrahydrofuran, tetrahydropyran, dioxane, and the like. The processes described herein can be monitored according to any suitable method known in the art. For example, product formation can be monitored by spectroscopic means, such as nuclear magnetic resonance spectroscopy (e.g., ¹ H or ¹³ C), infrared spectroscopy, or spectrophotometry (e.g., UV-visible); or by chromatography such as high performance liquid chromatography (HPLC) or thin layer chromatography (TLC) or other related techniques. As used herein, the terms “reacting” and “contacting” are used as known in the art and generally refers to the bringing together of chemical reagents in such a manner so as to allow their interaction at the molecular level to achieve a chemical or physical transformation. In some embodiments, the reacting involves two reagents, wherein one or more equivalents of second reagent are used with respect to the first reagent. The reacting steps of the processes described herein can be conducted for a time and under conditions suitable for preparing the identified product. The compounds of the present invention also include pharmaceutically acceptable salts of the compounds disclosed herein. As used herein, the term “pharmaceutically acceptable salt” refers to a salt formed by the addition of a pharmaceutically acceptable acid or base to a compound disclosed herein. As used herein, the phrase “pharmaceutically acceptable” refers to a substance that is acceptable for use in pharmaceutical applications from a toxicological perspective and does not adversely interact with the active ingredient. Pharmaceutically acceptable salts, including mono- and bi- salts, include, but are not limited to, those derived from organic and inorganic acids such as, but not limited to, acetic, lactic, citric, cinnamic, tartaric, succinic, fumaric, maleic, malonic, mandelic, malic, oxalic, propionic, hydrochloric, hydrobromic, phosphoric, nitric, sulfuric, glycolic, pyruvic, methanesulfonic, ethanesulfonic, toluenesulfonic, salicylic, benzoic, and similarly known acceptable acids. Lists of suitable salts are found in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418 and Journal of Pharmaceutical Science, 66, 2 (1977), each of which is incorporated herein by reference in their entireties. Preparation of compounds can involve the protection and deprotection of various chemical groups. The need for protection and deprotection, and the selection of appropriate protecting groups can be readily determined by one skilled in the art. The chemistry of protecting groups can be found, for example, in Greene, et al., Protective Groups in Organic Synthesis, 4d. Ed., Wiley & Sons, 2007, which is incorporated herein by reference in its entirety. Adjustments to the protecting groups and formation and cleavage methods described herein may be adjusted as necessary in light of the various substituents. The reactions of the processes described herein can be carried out in suitable solvents which can be readily selected by one of skill in the art of organic synthesis. Suitable solvents can be substantially nonreactive with the starting materials (reactants), the intermediates, or products at the temperatures at which the reactions are carried out, e.g., temperatures which can range from the solvent's freezing temperature to the solvent's boiling temperature. A given reaction can be carried out in one solvent or a mixture of more than one solvent. Depending on the particular reaction step, suitable solvents for a particular reaction step can be selected. In some embodiments, reactions can be carried out in the absence of solvent, such as when at least one of the reagents is a liquid or gas. Suitable solvents can include halogenated solvents such as carbon tetrachloride, bromodichloromethane, dibromochloromethane, bromoform, chloroform, bromochloromethane, dibromomethane, butyl chloride, dichloromethane, tetrachloroethylene, trichloroethylene, 1,1,1-trichloroethane, 1,1,2-trichloroethane, 1,1-dichloroethane, 2-chloropropane, α, α, α-trifluorotoluene, 1,2-dichloroethane, 1,2- dibromoethane, hexafluorobenzene, 1,2,4-trichlorobenzene, 1,2-dichlorobenzene, chlorobenzene, fluorobenzene, mixtures thereof and the like. Suitable solvents can include ether solvents such as: dimethoxymethane, tetrahydrofuran, 1,3-dioxane, 1,4-dioxane, furan, diethyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, triethylene glycol dimethyl ether, anisole, t-butyl methyl ether, mixtures thereof and the like. Suitable protic solvents can include, by way of example and without limitation, water, methanol, ethanol, 2-nitroethanol, 2-fluoroethanol, 2,2,2- trifluoroethanol, ethylene glycol, 1-propanol, 2-propanol, 2-methoxyethanol, 1- butanol, 2-butanol, i-butyl alcohol, t-butyl alcohol, 2-ethoxyethanol, diethylene glycol, 1-, 2-, or 3- pentanol, neo-pentyl alcohol, t-pentyl alcohol, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, cyclohexanol, benzyl alcohol, phenol, glycerol, mixtures thereof, and the like. Suitable aprotic solvents can include, by way of example and without limitation, tetrahydrofuran (THF), N,N-dimethylformamide (DMF), N,N- dimethylacetamide (DMA), 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU), 1,3-dimethyl-2-imidazolidinone (DMI), N-methylpyrrolidinone (NMP), formamide, N-methylacetamide, N-methylformamide, acetonitrile, dimethyl sulfoxide, propionitrile, ethyl formate, methyl acetate, hexachloroacetone, acetone, ethyl methyl ketone, ethyl acetate, sulfolane, N,N-dimethylpropionamide, tetramethylurea, nitromethane, nitrobenzene, hexamethylphosphoramide, mixtures thereof, and the like. Suitable hydrocarbon solvents include benzene, cyclohexane, pentane, hexane, toluene, cycloheptane, methylcyclohexane, heptane (e.g., n-heptane), ethylbenzene, m-, o-, or p-xylene, octane, indane, nonane, naphthalene, mixtures thereof, and the like. Supercritical carbon dioxide and ionic liquids can also be used as solvents. The reactions of the processes described herein can be carried out at appropriate temperatures which can be readily determined by the skilled artisan. Reaction temperatures will depend on, for example, the melting and boiling points of the reagents and solvent, if present; thermodynamics of the reaction (e.g., vigorously exothermic reactions may need to be carried out at reduced temperatures); and the kinetics of the reaction (e.g., a high activation energy barrier may need elevated temperatures). “Elevated temperature” refers to temperatures above room temperature (about 22 °C). The reactions of the processes described herein can be carried out in air or under an inert atmosphere. Typically, reactions containing reagents or products that are substantially reactive with air can be carried out using air-sensitive synthetic techniques that are well known to the skilled artisan. In some embodiments, preparation of compounds can involve the addition of acids or bases to affect, for example, catalysis of a desired reaction or formation of salt forms such as acid addition salts. Example acids can be inorganic or organic acids. Inorganic acids include hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, and nitric acid. Organic acids include formic acid, acetic acid, propionic acid, butanoic acid, benzoic acid, 4-nitrobenzoic acid, methanesulfonic acid, p-toluenesulfonic acid, benzenesulfonic acid, tartaric acid, trifluoroacetic acid, propiolic acid, butyric acid, 2- butynoic acid, vinyl acetic acid, pentanoic acid, hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid and decanoic acid. Example bases include alkali metal hydroxides (e.g., lithium hydroxide, sodium hydroxide, and potassium hydroxide), and alkali metal carbonate (e.g., lithium carbonate, sodium carbonate, and potassium carbonate). Some example strong bases include, but are not limited to, hydroxide, alkoxides, metal amides, metal hydrides, metal dialkylamides and arylamines, wherein; alkoxides include lithium, sodium and potassium salts of methyl, ethyl and t-butyl oxides; metal amides include sodium amide, potassium amide and lithium amide; metal hydrides include sodium hydride, potassium hydride and lithium hydride; and metal dialkylamides include sodium and potassium salts of methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, trimethylsilyl and cyclohexyl substituted amides. The present invention also includes salt forms of the compounds described herein. Examples of salts (or salt forms) include, but are not limited to, mineral or organic acid salts of basic residues such as amines, alkali or organic salts of acidic residues such as carboxylic acids, and the like. Generally, the salt forms can be prepared by reacting the free base or acid with stoichiometric amounts or with an excess of the desired salt-forming inorganic or organic acid or base in a suitable solvent or various combinations of solvents. Lists of suitable salts are found in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p.1418, the disclosure of which is hereby incorporated by reference in its entirety. Upon carrying out preparation of compounds according to the processes described herein, the usual isolation and purification operations such as concentration, filtration, extraction, solid-phase extraction, recrystallization, chromatography, and the like may be used, to isolate the desired products. In some embodiments, the compounds of the invention, and salts thereof, are substantially isolated. By “substantially isolated” is meant that the compound is at least partially or substantially separated from the environment in which it was formed or detected. Partial separation can include, for example, a composition enriched in the compound of the invention. Substantial separation can include compositions containing at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% by weight of the compound of the invention, or salt thereof. Methods for isolating compounds and their salts are routine in the art. In some embodiments, ruxolitinib), intermediates for preparing ruxolitinib reagents, and salts thereof can include both anhydrous forms of that substance and solvated/hydrated forms of that substance. Different forms of the same substance have different bulk properties relating to, for example, hygroscopicity, solubility, stability, and the like. Forms with high melting points often have good thermodynamic stability which is advantageous in prolonging shelf-life drug formulations comprising the solid form. Forms with lower melting points often are less thermodynamically stable, but are advantageous in that they have increased water solubility, translating to increased drug bioavailability. Forms that are weakly hygroscopic are desirable for their stability to heat and humidity and are resistant to degradation during long storage. In some embodiments, the solid form of Compound 1, intermediates for preparing Compound 1, and salts thereof are crystalline. In some embodiments, a Compound 1 salt (e.g., Compound 1 phosphate) provided herein is crystalline. As used herein, “crystalline” or “crystalline form” is meant to refer to a certain lattice configuration of a crystalline substance. Different crystalline forms of the same substance typically have different crystalline lattices (e.g., unit cells) which are attributed to different physical properties that are characteristic of each of the crystalline forms. In some instances, different lattice configurations have different water or solvent content. The different solid forms and salt forms thereof can be identified by solid state characterization methods such as by X-ray powder diffraction (XRPD). Other characterization methods such as differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), dynamic vapor sorption (DVS), solid state NMR, and the like further help identify the form as well as help determine stability and solvent/water content. An XRPD pattern of reflections (peaks) is typically considered a fingerprint of a particular crystalline form. It is well known that the relative intensities of the XRPD peaks can widely vary depending on, inter alia, the sample preparation technique, crystal size distribution, various filters used, the sample mounting procedure, and the particular instrument employed. In some instances, new peaks may be observed or existing peaks may disappear, depending on the type of the instrument or the settings. As used herein, the term “peak” refers to a reflection having a relative height/intensity of at least about 4% of the maximum peak height/intensity. Moreover, instrument variation and other factors can affect the 2-theta values. Thus, peak assignments, such as those reported herein, can vary by plus or minus about 0.2° (2-theta), and the term “substantially” and “about” as used in the context of XRPD herein is meant to encompass the above-mentioned variations. In the same way, temperature readings in connection with DSC, TGA, or other thermal experiments can vary about ± 3 °C depending on the instrument, particular settings, sample preparation, etc. Accordingly, a crystalline form reported herein having a DSC thermogram “substantially” as shown in any of the Figures or the term “about” is understood to accommodate such variation. Generally, the term “about” means ± 10%. In some embodiments, the term “about” means ± 5%. In some embodiments, the solid forms and salt forms are substantially isolated. By “substantially isolated” is meant that the solid form, salt form or crystalline form thereof is at least partially or substantially separated from the environment in which it was formed or detected. Partial separation can include, for example, a composition enriched in the solid forms and salt forms. Substantial separation can include compositions containing at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% by weight of the solid forms and salt forms. Methods for isolating solid forms and salt forms thereof are routine in the art. In some embodiments, the solid forms and salt forms described herein can be found together with other substances such as water and solvents (e.g., hydrates and solvates) or can be isolated. The phrase “pharmaceutically acceptable” is employed herein to refer to those salts, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio. The salt forming reactions described herein can be carried out at appropriate temperatures which can be readily determined by the skilled artisan. Reaction temperatures will depend on, for example, the melting and boiling points of the reagents and solvent, if present; thermodynamics of the reaction (e.g., vigorously exothermic reactions may need to be carried out at reduced temperatures); and the kinetics of the reaction (e.g., a high activation energy barrier may need elevated temperatures). The expressions, “ambient temperature” and “room temperature” or “rt” as used herein, are understood in the art, and refer generally to a temperature, e.g., a reaction temperature, that is about the temperature of the room in which the reaction is carried out, for example, a temperature from about 20 ºC to about 30 ºC. The protecting groups (e.g., P ¹ P ² ) described herein include, but are not limited to, the protecting groups for amines delineated in Wuts and Greene, Protective Groups in Organic Synthesis, 4th ed., John Wiley & Sons: New Jersey, pages 696-887 (and, in particular, pages 872-887) (2007), which is incorporated herein by reference in its entirety. Examples of protecting group as described herein include CH ₂ OC(=O)C(CH ₃ ) ₃ , CH ₂ OCH ₂ CH ₂ Si(CH ₃ ) _3, benzyloxycarbonyl (Cbz), 2,2,2- trichloroethoxycarbonyl (Troc), 2-(trimethylsilyl)ethoxycarbonyl (Teoc), 2-(4- trifluoromethylphenylsulfonyl)ethoxycarbonyl (Tsc), t-butoxycarbonyl (BOC), 1- adamantyloxycarbonyl (Adoc), 2-adamantylcarbonyl (2-Adoc), 2,4-dimethylpent-3- yloxycarbonyl (Doc), cyclohexyloxycarbonyl (Hoc), 1,1-dimethyl-2,2,2- trichloroethoxycarbonyl (TcBOC), vinyl, 2-chloroethyl, 2-phenylsulfonylethyl, allyl, benzyl, 2-nitrobenzyl, 4-nitrobenzyl, diphenyl-4-pyridylmethyl, N’,N’- dimethylhydrazinyl, methoxymethyl, t-butoxymethyl (Bum), benzyloxymethyl (BOM), 2-tetrahydropyranyl (THP), tri(C _1-4 alkyl)silyl (e.g., tri(isopropyl)silyl or t- butyldimethylsilyl), 1,1-diethoxymethyl, 2-(trimethylsilyl)ethoxymethyl (SEM), N- pivaloyloxymethyl (POM), p-nitrophenylsulfonyl, p-toluenesulfonyl, phenylsulfonyl, methanesulfonyl, and the like. In some embodiments, the protecting group is tri(C _1-4 alkyl)silyl (e.g., tri(isopropyl)silyl or t-butyldimethylsilyl). In some embodiments, the protecting group is t-butyldimethylsilyl. In some embodiments, the protecting group is p-toluenesulfonyl. In some embodiments, one or more constituent atoms of the compounds (products or synthetic intermediates) presented herein can be replaced or substituted with isotopes of the atoms in natural or non-natural abundance. In some embodiments, the compound includes at least one deuterium atom. For example, in some embodiments one or more hydrogen atoms in a compound presented herein can be replaced or substituted by deuterium (e.g., one or more hydrogen atoms of a C _1-6 alkyl group can be replaced by deuterium atoms, such as –CD3 being substituted for –CH ₃ ). In some embodiments, the compound includes two or more deuterium atoms. In some embodiments, the compound includes 1-2, 1-3, 1-4, 1-5, 1-6, 1-7, or 1-8 deuterium atoms. In some embodiments, one or more hydrogen atoms of the ruxolitinib, or the salt thereof, are replaced by deuterium atoms. In some embodiments, the CH ₂ groups of the cyclopentyl ring of the ruxolitinib, or the salt thereof, are replaced by CD2 groups. In some embodiments, one or more hydrogen atoms of the compound of formula 3, or the salt thereof, are replaced by deuterium atoms. In some embodiments, the CH ₂ groups of the cyclopentyl ring of the compound of formula 3, or the salt thereof, are replaced by CD ₂ groups. In some embodiments, one or more hydrogen atoms of the salt of formula 3a are replaced by deuterium atoms. In some embodiments, the CH ₂ groups of the cyclopentyl ring of the salt of formula 3a are replaced by CD ₂ groups. The invention will be described in greater detail by way of specific examples. The following examples are offered for illustrative purposes, and are not intended to limit the invention in any manner. Those of skill in the art will readily recognize a variety of noncritical parameters which can be changed or modified to yield essentially the same results. Examples (R)-3-(4-(7H-Pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)- 3- cyclopentylpropanenitrile (Compound 1) and its phosphate salt were prepared according to the scheme below. Scheme 2

Note that when Compound 2a is a chloride salt, it could be isolated as Compound 2 chloride (Compound 2c) or Compound 2 chloride hydrochloride (Compound 2d): (2c) (2d). As described in the following examples, by LCMS, MS data of about m/e 244 was obtained for compound 2a, which means compound 2 without the anion was detected. Embodiments 1. A process of preparing ruxolitinib, or a salt thereof, comprising: reacting a compound of formula 3: or a salt thereof, with a reagent which is a salt of formula 2a, or a salt thereof, or a compound of formula 2b: wherein X- is a counter anion. 2. The process of embodiment 1, wherein the compound of formula 3, or the salt thereof, is a chiral salt of the compound of formula 3. 3. The process of embodiment 2, wherein the chiral salt is prepared by reacting the compound of formula 3 with an optically active form of an acid selected from mandelic acid, 2-chloromandelic acid, camphorsulfonic acid, tartaric acid, lactic acid, malic acid, 3-bromocamphor-8-sulfonic acid, 3-bromocamphor-10-sulfonic acid, 10- camphorsulfonic acid, dibenzoyl tartaric acid, di-p-toluoyltartaric acid, 2-amino-7,7- dimethylbicyclop[2,2,1]heptan-1-methylene sulfonic acid, and 2-acrylamide-7,7- dimethylbicyclo[2,2,1] heptan-1-methylene sulfonic acid. 4. The process of embodiment 2, wherein the chiral salt is the L-(+)-tartrate salt of the compound of formula 3. 5. The process of embodiment 2, wherein the compound of formula 3, or the salt thereof, has formula 3a: 6. The process of any one of embodiments 1-6, wherein from about 1 to about 1.5 molar equivalent of the reagent is utilized relative to the compound of formula 3, or salt thereof. 7. The process of any one of embodiments 1-6, wherein the reacting of the reagent with the compound of formula 3, or the salt thereof, is carried out in a solvent component S1. 8. The process of embodiment 7, wherein the solvent component S1 comprises water. 9. The process of embodiment 7, wherein the solvent component S1 comprises an alcohol. 10. The process of embodiment 7, wherein the solvent component S1 comprises ethanol. 11. The process of embodiment 7 or 8, wherein the solvent component S1 comprises dimethylformamide. 12. The process of embodiment 7 or 8, wherein the solvent component S1 comprises water, an alcohol or a combination thereof. 13. The process of any one of embodiments 1-12, wherein the reagent is the salt of formula 2a or a compound of formula 2b. 14. The process of any one of embodiments 1-13, wherein the reagent is the salt of formula 2a. 15. The process of any one of embodiments 1-13, wherein X- is selected from Cl-, Br-, I-, BF4-, PF ₆ -, AsF ₆ -, SbF ₆ -, and ClO ₄ -. 16. The process of any one of embodiments 1-13, wherein X- is selected from Cl-, BF4-, PF ₆ -, AsF ₆ -, SbF ₆ -, and ClO ₄ -. 17. The process of any one of embodiments 1-13, wherein X- is BF4-. 18. The process of any one of embodiments 1-13, wherein X- is PF ₆ -. 19. The process of any one of embodiments 1-13, wherein X- is AsF ₆ -. 20. The process of any one of embodiments 1-13, wherein X- is SbF ₆ -. 21. The process of any one of embodiments 1-13, wherein X- is ClO ₄ -. 22. The process of any one of embodiments 1-13, wherein X- is Cl-. 23. The process of any one of embodiments 1-12, wherein the reagent is the hydrochloric acid salt of the salt of formula 2a, wherein X- is Cl-. 24. The process of any one of embodiments 1-12, wherein the reagent is the compound of formula 2b. 25. The process of any one of embodiments 1-24, wherein the compound of formula 2b is prepared by a process comprising reacting the salt of formula 2a with a base B1. 26. The process of embodiment 25, wherein the reacting of the salt of formula 2a with the base B1 is conducted in a solvent component S2 comprising water. 27. The process of embodiment 25 or 26, wherein the base B1 is a strong base. 28. The process of any one of embodiments 25-27, wherein the base B1 is a hydroxide. 29. The process of any one of embodiments 25-28, wherein the base B1 is an alkali metal hydroxide. 30. The process of any one of embodiments 25-29, wherein the base B1 is sodium hydroxide. 31. The process of any one of embodiments 25-30, wherein from about 10 to about 15 molar equivalents of the base B1 is utilized relative to the salt of formula 2a or the salt thereof. 32. The process of any one of embodiments 25-30, wherein from about 12 molar equivalents of the base B1 is utilized relative to the salt of formula 2a, or salt thereof. 33. The process of any one of embodiments 25-32, wherein the reacting of the salt of formula 2a with the base B1 is conducted at a temperature of from about -10 °C to about 60 °C. 34. The process of any one of embodiments 1-33, wherein the salt of formula 2a or the compound of formula 2b is prepared by a process comprising: reacting the compound of formula 1a: or a salt thereof, with a Vilsmeier reagent formed from dimethylformamide. 35. The process of any one of embodiments 1-33, wherein the salt of formula 2a or the compound of formula 2b is prepared by a process comprising: reacting the compound of formula 5a: or a salt thereof, with a Vilsmeier reagent formed from dimethylformamide. 36. The process of embodiment 35, wherein the compound of formula 5a, or the salt thereof, is a salt. 37. The process of embodiment 35 or 36, wherein the compound of formula 5a, or the salt thereof, is the sodium salt. 38. The process of any one of embodiments 34-37, wherein the reacting with the Vilsmeier reagent produces a compound of formula 2c: 39. The process of embodiment 38, wherein after the reacting with a Vilsmeier reagent, the compound of formula 2c is reacted with a salt of formula M ⁺ X-, wherein M ⁺ is a counter cation. 40. The process of any one of embodiments 34-39, wherein the Vilsmeier reagent is prepared by a process comprising reacting dimethylformamide with a chlorinating agent. 41. The process of embodiment 40, wherein the chlorinating agent is selected from oxalyl chloride, phosphorus oxychloride, triphosgene, thionyl chloride, sulfuryl chloride, and phosphorus pentachloride. 42. The process of embodiment 40, wherein the chlorinating agent is selected from oxalyl chloride, phosphorus oxychloride, and triphosgene. 43. The process of embodiment 40, wherein the chlorinating agent is oxalyl chloride. 44. The process of embodiment 40, wherein the chlorinating agent is phosphorus oxychloride. 45. The process of embodiment 40, wherein the chlorinating agent is triphosgene. 46. The process of any one of embodiments 40-45, wherein from about 1 to about 5 molar equivalents of the chlorinating agent are utilized relative to the compound of formula 1a or 5a, or the salt thereof. 47. The process of any one of embodiments 40-45, wherein from about 1 to about 4 molar equivalents of the chlorinating agent are utilized relative to the compound of formula 1a or 5a, or the salt thereof. 48. The process of any one of embodiments 40-45, wherein from about 1 to about 3 molar equivalents of the chlorinating agent are utilized relative to the compound of formula 1a or 5a, or the salt thereof. 49. The process of any one of embodiments 34-48, wherein from about 10 to about 25 molar equivalents of dimethylformamide are utilized relative to the compound of formula 1a or 5a, or the salt thereof. 50. The process of any one of embodiments 34-48, wherein from about 10 to about 20 molar equivalents of dimethylformamide are utilized relative to the compound of formula 1a or 5a, or the salt thereof. 51. The process of any one of embodiments 34-48, wherein from about 10 to about 15 molar equivalents of dimethylformamide are utilized relative to the compound of formula 1a or 5a, or the salt thereof. 52. The process of any one of embodiments 34-48, wherein from about 11 to about 14 molar equivalents of dimethylformamide are utilized relative to the compound of formula 1a or 5a, or the salt thereof. 53. The process of any one of embodiments 34-48, wherein from about 11 to about 13 molar equivalents of dimethylformamide are utilized relative to the compound of formula 1a or 5a, or the salt thereof. 54. The process of any one of embodiments 34-53, wherein the preparation of the Vilsmeier reagent is carried out in a solvent component S3. 55. The process of embodiment 54, wherein the solvent component S3 comprises an organic solvent. 56. The process of embodiment 54 or 55, wherein the solvent component S3 comprises a polar aprotic solvent. 57. The process of any one of embodiments 54-56, wherein the solvent component S3 comprises acetonitrile, dimethyformamide, or a combination thereof. 58. The process of any one of embodiments 34-57, wherein the Vilsmeier reagent is prepared at a temperature between from about -10 °C to about 60 °C. 59. The process of any one of embodiments 34-57, wherein the Vilsmeier reagent is prepared at a temperature between from about -10 °C to about 30 °C. 60. The process of any one of embodiments 34-57, wherein the Vilsmeier reagent is prepared at a temperature between from about room temperature to about 60 °C. 61. The process of any one of embodiments 34-60, wherein the reacting of the compound of formula 1a or 5a, or the salt thereof with the Vilsmeier reagent is carried out at a temperature of from about 40 °C to about 100 °C. 62. The process of any one of embodiments 34-60, wherein the reacting of the compound of formula 1a or 5a, or the salt thereof with the Vilsmeier reagent is carried out at a temperature of from about 70 °C to about 100 °C. 63. The process of any one of embodiments 34-60, wherein the reacting of the compound of formula 1a or 5a, or the salt thereof with the Vilsmeier reagent is carried out at a temperature of from about 40 °C to about 60 °C. 64. The process of any one of embodiments 34-63, wherein the product of the reacting with the Vilsmeier reagent has formula 2d: 65. The process of any one of embodiments 1-64, wherein the salt of formula 2a is formed by a process comprising: reacting the salt of formula 2c: with a salt of formula M ⁺ X-, wherein: M ⁺ is a counter cation; and X- is a counter anion other than Cl- 66. The process of embodiment 65, wherein M ⁺ is an alkali metal counter cation. 67. The process of embodiment 65, wherein M ⁺ is Li ⁺ , Na ⁺ or K ⁺ . 68. The process of embodiment 65, wherein M ⁺ is Na ⁺ . 69. The process of any one of embodiments 65-68, wherein X- is selected from Br- , I-, BF4-, PF ₆ -, AsF ₆ -, SbF ₆ -, and ClO ₄ -. 70. The process of any one of embodiments 38-69 wherein the salt of formula 2c is produced by a process comprising: reacting a salt of formula 2d: with a base. 71. The process of any one of embodiments 1-14, 24, and 70, wherein the compound of formula 2b is prepared by a process comprising reacting a salt of formula 2d with a base B2. 72. The process of embodiment 71, wherein (i) the reacting of the salt of formula 2d with a base B2 and (ii) the reacting of the salt of formula 2a with the compound of formula 3 are conducted in a single pot. 73. The process of embodiment 71 or 72, wherein the reacting of the salt of formula 2d with a base B2 is conducted in a solvent component comprising water. 74. The process of any one of embodiments 71-73, wherein the base B2 is a strong base. 75. The process of any one of embodiments 71-74, wherein the base B2 is a hydroxide base. 76. The process of any one of embodiments 71-75, wherein the base B2 is an alkali metal hydroxide. 77. The process of any one of embodiments 71-76, wherein the base B2 is sodium hydroxide. 78. The process of any one of embodiments 71-77, wherein the reacting of the salt of formula 2d with a base B2 is conducted at a temperature of from about -10 °C to about 15 °C. 79. The process of embodiment 34, wherein the compound of formula 1a, or the salt thereof, is the hydrochloride salt. 80. The process of embodiment 34 or 79 wherein the compound of formula 1a, or the salt thereof, is prepared by a process comprising: deprotecting a compound of formula 1aP: 1aP wherein P ¹ is an amino protecting group. 81. The process of embodiment 80, wherein P ¹ is selected from (R ¹ ) ₃ Si, wherein R ¹ is C _1-6 alkyl. 82. The process of embodiment 81, wherein R ¹ is methyl, ethyl, propyl, isopropyl, butyl or t-butyl. 83. The process of any one of embodiments 80-82, wherein P ¹ is t- butyldimethylsilyl. 84. The process of any one of embodiments 80-83, wherein the deprotecting is carried out by reacting the compound of formula 1aP with a base B3. 85. The process of embodiment 84, wherein the base B3 is a hydroxide base. 86. The process of embodiment 84 or 85, where the base B3 is ammonium hydroxide. 87. The process of any one of embodiments 80-86, wherein the deprotecting is carried out in a solvent component S4. 88. The process of embodiment 87, wherein the solvent component S4 comprises a polar protic solvent. 89. The process of embodiment 87 or 88, wherein the solvent component S4 comprises an alcohol. 90. The process of any one of embodiments 87-89, wherein the solvent component S4 comprises formula C _1-6 alkyl-OH. 91. The process of any one of embodiments 87-90, wherein the solvent component S4 comprises methanol. 92. The process of any one of embodiments 80-91, wherein the compound of formula 1aP is prepared by a process comprising: reacting a compound of formula 2P: with MeMgBr in the presence of a Grignard catalyst, wherein P ¹ is an amino protecting group. 93. The process of embodiment 92, wherein the catalyst is an iron catalyst. 94. The process of embodiment 92 or 93, wherein the iron catalyst is iron(III) acetylacetonate. 95. The process of any one of embodiments 92-94, wherein from about 1 to about 2 molar equivalents of MeMgCl are utilized relative to the compound of formula 2P. 96. The process of any one of embodiments 92-95, wherein from about 1% to about 10% molar equivalents of the catalyst are utilized relative to the compound of formula 2P. 97. The process of any one of embodiments 92-96, wherein the reacting of the compound formula 2P with MeMgCl is carried out in a solvent component S5. 98. The process of embodiment 97, wherein the solvent component S5 comprises a di-C _1-6 alkyl ether or a 4-10 membered heterocycloalkyl ether. 99. The process of embodiment 97 or 98, wherein the solvent component S5 comprises a tetrahydrofuran. 100. The process of any one of embodiments 92-99, wherein the reacting of the compound formula 2P with MeMgCl is carried out at a temperature of from about -10 °C to about 30 °C. 101. The process of any one of embodiments 91-100, wherein the compound of formula 2P is prepared by a process comprising: protecting a compound of formula 12a: to form the compound of formula 2P. 102. The process of embodiment 101, wherein the protecting comprise reacting the compound of formula 12a with an alkali metal hydride and P ¹ -Y, wherein Y is halo. 103. The process of embodiment 102, wherein P ¹ -Y is (R ¹ )3Si-Y, wherein Y is halo and R ¹ is C _1-6 alkyl. 104. The process of embodiment 103, wherein P ¹ is (R ¹ ) ₃ Si, wherein R ¹ is C _1-6 alkyl. 105. The process of embodiment 102 and 103, wherein R ¹ is methyl, ethyl, propyl, isopropyl, butyl or t-butyl. 106. The process of any one of embodiments 102-105, wherein P ¹ is t- butyldimethylsilyl. 107. The process of any one of embodiments 102-106, wherein the alkali metal hydride is sodium hydride. 108. The process of any one of embodiments 102-107, wherein from about 1 to about 2 molar equivalents of the alkali metal hydride is utilized relative to the compound of formula 12a. 109. The process of any one of embodiments 102-108, wherein from about 1 to about 2 molar equivalents of P ¹ -Y is utilized relative to the compound of formula 12a. 110. The process of any one of embodiments 102-109, wherein the reacting of the compound of formula 12a with the alkali metal hydride and P ¹ -Y is carried out at a temperature of about -10 °C to about 20 °C. 111. The process of any one of embodiments 102-110, wherein the reacting of the compound of formula 12a with the alkali metal hydride and P ¹ -Y is carried out in a solvent component S6, wherein the solvent component S6 comprises an organic solvent. 112. The process of embodiment 111, wherein the solvent component S6 comprises a di-C _1-6 alkyl ether or a 4-10 membered heterocycloalkyl ether. 113. The process of embodiment 111 or 112, wherein the solvent component S6 comprises a tetrahydrofuran. 114. The process of any one of embodiments 34 and 79-113, wherein the compound of formula 1a, or the salt thereof, is prepared by a process comprising: reducing a compound of formula 23P: wherein P ² is an amino protecting group. 115. The process of embodiment 114, wherein the reducing of the compound of formula 23P is accomplished by a process comprising reacting the compound of formula 23P with hydrogen gas in the presence of a catalyst. 116. The process of embodiment 115, wherein the catalyst is Pd ⁰ on carbon. 117. The process of embodiment 115 or 116, wherein the amount of the catalyst relative to the compound of formula 23P is about 5% to about 15% by weight. 118. The process of any one of embodiments 115-117, wherein the reacting of the compound of formula 23P with hydrogen and the catalyst is carried out at a temperature of about 40 °C to about 70 °C. 119. The process of any one of embodiments 115-118, wherein the reacting of the compound of formula 23aP with hydrogen and the catalyst is carried out in a solvent component S7. 120. The process of embodiment 119, wherein the solvent component S7 comprises a polar protic solvent. 121. The process of embodiment 119 or 120, wherein the solvent component S7 comprises an alcohol. 122. The process of any one of embodiments 119-121, wherein the solvent component S7 comprises formula C _1-6 alkyl-OH. 123. The process of any one of embodiments 119-122, wherein the solvent component S7 comprises methanol. 124. The process of any one of embodiments 114-123, wherein the compound of formula 23P is prepared by a process comprising: reacting a compound of formula 22P: with MeMgBr in the presence of a Grignard catalyst, wherein P ² is an amino protecting group. 125. The process of embodiment 124, wherein the catalyst is an iron catalyst. 126. The process of embodiment 125 wherein the iron catalyst is iron(III) acetylacetonate. 127. The process of any one of embodiments 124-126, wherein from about 1 to about 2 molar equivalents of MeMgCl is utilized relative to the compound of formula 22P. 128. The process of any one of embodiments 124-127, wherein from about 1% to about 10% molar equivalents of the catalyst are utilized relative to the compound of formula 22P. 129. The process of any one of embodiments 124-128, wherein the reacting of the compound formula 22P with MeMgCl is carried out in a solvent component S8. 130. The process of embodiment 129, wherein the solvent component S8 comprises a di-C _1-6 alkyl ether or a 4-10 membered heterocycloalkyl ether. 131. The process of embodiment 129 or 130, wherein the solvent component S8 comprises a tetrahydrofuran. 132. The process of any one of embodiments 124-131, wherein the reacting of the compound formula 2P with MeMgCl is carried out at a temperature of from about -10 °C to about 30 °C. 133. The process of any one of embodiments 124-132, wherein the compound of formula 22P is prepared by a process comprising: protecting a compound of formula 22a: to form the compound of formula 22P. 134. The process of embodiment 133, wherein the protecting comprise reacting the compound of formula 22a with an alkali metal hydride and P ² -Y, wherein Y is halo. 135. The process of embodiment 134, wherein P ² is (R ¹ )3Si, wherein R ¹ is C _1-6 alkyl. 136. The process of embodiment 135, wherein R ¹ is methyl, ethyl, propyl, isopropyl, butyl or t-butyl. 137. The process of any one of embodiments 134-136, wherein P ² is t- butyldimethylsilyl. 138. The process of any one of embodiments 134-137, wherein the alkali metal hydride is sodium hydride. 139. The process of any one of embodiments 134-138, wherein from about 1 to about 2 molar equivalents of the alkali metal hydride is utilized relative to the compound of formula 22a. 140. The process of any one of embodiments 134-139, wherein from about 1 to about 2 molar equivalents of P ² -Y is utilized relative to the compound of formula 22a. 141. The process of any one of embodiments 134-140, wherein the reacting of the compound of formula 22a with the alkali metal hydride and P ² -Y is carried out at a temperature of about -10 °C to about 20 °C. 142. The process of any one of embodiments 134-141, wherein the reacting of the compound of formula 22a with the alkali metal hydride and P ² -Y is carried out in a solvent component S9, wherein the solvent component S9 comprises an organic solvent. 143. The process of embodiment 142, wherein the solvent component S9 comprises a di-C _1-6 alkyl ether or a 4-10 membered heterocycloalkyl ether. 144. The process of embodiment 142 or 143, wherein the solvent component S9 comprises a tetrahydrofuran. 145. The process of any one of embodiments 34 and 79-113, wherein the compound of formula 1a, or the salt thereof, is prepared by a process comprising: reacting a compound of formula 18a: with an acid A1 to form the compound of formula 1a. 146. The process of embodiment 145, wherein the acid A1 is a strong acid. 147. The process of embodiment 145 or 146, wherein the acid A1 is hydrochloric acid. 148. The process of any one of embodiments 145-147, wherein the reacting of the compound of formula 18a with the acid A1 is carried out in a solvent component S10, wherein the solvent component S10 comprises a polar protic solvent. 149. The process of embodiment 148, wherein the solvent component S10 comprises an alcohol. 150. The process of embodiment 148 or 149, wherein the solvent component S10 comprises formula C _1-6 alkyl-OH. 151. The process of any one of embodiments 148-150, wherein the solvent component S10 comprises isopropyl alcohol. 152. The process of any one of embodiments 148-151, wherein the compound of formula 18a, or a salt thereof, is prepared by a process comprising: reacting a compound of formula 17a: with formamidine acetate and triethyl orthoformate to form the compound of formula 17a. 153. The process of embodiment 152, wherein from about 10 to about 15 molar equivalents of formamidine acetate is utilized relative to the compound of formula 17a is about 10 to about 15. 154. The process of embodiment 152 or 153, wherein from about 6 to about 10 molar equivalents of triethyl orthoformate is utilized relative to the compound of formula 17a. 155. The process of any one of embodiments 152-154, wherein the reacting of the compound of formula 17a with formamidine acetate and triethyl orthoformate is carried out at a temperature of about 100 °C to about 150 °C. 156. The process of any one of embodiments 152-155, wherein the reacting of the compound of formula 17a with formamidine acetate and triethyl orthoformate is carried out in a solvent component S11, wherein the solvent component S11 comprises a polar protic solvent. 157. The process of embodiment 156, wherein the solvent component S11 comprises an alcohol. 158. The process of embodiment 156 or 157, wherein the solvent component S11 comprises formula C _1-6 alkyl-OH. 159. The process of any one of embodiments 156-158, wherein the solvent component S11 comprises 1-butanol. 160. The process of any one of embodiments 152-159, wherein the compound of formula 17a, or a salt thereof, is prepared by a process comprising: reacting a compound of formula 20a: with a compound of formula 21a: to form the compound of formula 17a. 161. The process of embodiment 160, wherein from about 0.4 to about 1 molar equivalents of the compound of formula 21a is utilized relative to the compound of formula 20a. 162. The process of embodiment 160 or 161, wherein the reacting of the compound of formula 20a with the compound of formula 21a is carried out at room temperature. 163. The process of any one of embodiments 160-162, wherein the reacting of the compound of formula 20a with the compound of formula 21a is carried out in a solvent component S12, wherein the solvent component S12 comprises a polar aprotic solvent. 164. The process of embodiment 163, wherein the solvent component S12 comprises dimethylformamide. 165. The process of any one of embodiments 160-164, wherein the compound of formula 20a, or a salt thereof, is prepared by a process comprising: reacting a compound of formula 19a: with bromo-1,1-dimethoxyethane and a base B4 to form the compound of formula 20a. 166. The process of embodiment 165, wherein the base B4 is an alkali metal carbonate. 167. The process of embodiment 165 or 166, wherein the base B4 is cesium carbonate. 168. The process of any one of embodiments 165-167, wherein from about 1 to about 2 molar equivalents of the base B4 is utilized relative to the compound of formula 19a. 169. The process of any one of embodiments 165-168, wherein from about 1 to about 2 molar equivalents of bromo-1,1-dimethoxyethane is utilized relative to the compound of formula 19a. 170. The process of any one of embodiments 165-169, wherein the reacting of the compound of formula 19a with bromo-1,1-dimethoxyethane is carried out at a temperature of about 70 °C to about 100 °C. 171. The process of any one of embodiments 165-170, wherein the reacting of the compound of formula 19a with bromo-1,1-dimethoxyethane is carried out in a solvent component S13, wherein the solvent component S13 comprises a polar aprotic solvent. 172. The process of embodiment 171, wherein the solvent component S13 is dimethylformamide. 173. The process of any one of embodiments 152-159, wherein the compound of formula 17a, or a salt thereof, is prepared by a process comprising: reacting a compound of formula 16a: with ethyl acetate and a base B5 to form the compound of formula 17a. 174. The process of embodiment 173, wherein the base B5 is an alkali metal alkoxide. 175. The process of embodiment 173 or 174, wherein the base B5 is potassium tert- butoxide. 176. The process of any one of embodiments 173-175, wherein from about 1 to about 3 molar equivalents of the base B5 is utilized relative to the compound of formula 16a. 177. The process of any one of embodiments 173-176, wherein from about 1 to about 2 molar equivalents of ethyl acetate is utilized relative to the compound of formula 16a. 178. The process of any one of embodiments 172-177, wherein the reacting of the compound of formula 17a with ethyl acetate and a base B5 is carried out at room temperature. 179. The process of any one of embodiments 172-178, wherein the reacting of the compound of formula 17a with ethyl acetate and a base B5 is carried out in a solvent component S14, wherein the solvent component S14 comprises an organic solvent. 180. The process of embodiment 179, wherein the solvent component S14 comprises a di-C _1-6 alkyl ether or a 4-10 membered heterocycloalkyl ether. 181. The process of embodiment 179 or 180 wherein the solvent component S14 comprises a tetrahydrofuran. 182. The process of any one of embodiments 35-79, wherein the compound of formula 5a, or the salt thereof, is prepared by a process comprising: hydrolyzing a compound of formula 27a: in water in the presence of a base B6. 183. The process of embodiment 182, wherein the base B6 is an alkali metal hydroxide. 184. The process of embodiment 182 or 183, wherein the base B6 is sodium hydroxide. 185. The process of any one of embodiments 182-184, wherein from about 1 to about 2 molar equivalents of the base B6 is utilized relative to the compound of formula 27a. 186. The process of any one of embodiments 182-185, wherein the hydrolyzing of the compound of formula 27a is carried out at room temperature. 187. The process of any one of embodiments 182-186, wherein the hydrolyzing of the compound of formula 27a is carried out in a solvent component S15, wherein the solvent component S15 comprises an organic solvent. 188. The process of embodiment 187, wherein the solvent component S15 comprises tetrahydrofuran, acetone, or a combination thereof. 189. The process of any one of embodiments 182-188, wherein the compound of formula 5a, or the salt thereof, is the sodium salt of the compound of formula 5a. 190. The process of any one of embodiments 182-188, wherein the compound of formula 5a, or the salt thereof, is the compound of formula 5a. 191. The process of embodiment 190, wherein the compound of formula 5a is prepared by a process comprising reacting the sodium salt of the compound of formula 5a with a strong acid A2. 192. The process of embodiment 191, wherein the strong acid A2 is hydrochloric acid. 193. The process of embodiment 191 or 192, wherein (a) the reacting of the sodium salt of compound of formula 5a with a strong acid A2 and (b) the hydrolyzing of the sodium salt of the compound of formula 27a is carried out in a single pot. 194. The process of any one of embodiments 182-193, wherein the compound of formula 27a is prepared by a process comprising: reacting a compound of formula 26P: with a strong acid A3, wherein P ¹ is an amino protecting group. 195. The process of embodiment 194, wherein P ¹ is p-toluenesulfonyl 196. The process of embodiment 194 or 195, wherein A3 is hydrochloric acid. 197. The process of any one of embodiments 194-196, wherein the reacting of the compound of formula 26P with a strong acid A3 is carried out at room temperature. 198. The process of any one of embodiments 194-197, wherein the reacting of the compound of formula 26P with a strong acid A3 is carried out in a solvent component S16. 199. The process of any one of embodiments 194-198 wherein the solvent component S16 comprises formula C _1-6 alkyl-OH. 200. The process of embodiment 199, wherein the solvent component S16 comprises ethanol. 201. The process of any one of embodiments 194-200, wherein the compound of formula 26P is prepared by a process comprising: reacting a compound of formula 25P: with alkali metal alkoxide B8 to form the compound of formula 26P, wherein P ¹ is an amino protecting group. 202. The process of embodiment 201, wherein about 0.1 molar equivalents of alkali metal alkoxide B8 is utilized relative to the compound of formula 25P. 203. The process of embodiments 201 or 202, wherein the reacting of the compound of formula 25P with alkali metal alkoxide B8 is carried out at room temperature. 204. The process of any one of embodiments 201-202, wherein the reacting of the compound of formula 25P with alkali metal alkoxide B8 is carried out in a solvent component S17, wherein the solvent component S17 comprises a polar protic solvent. 205. The process of any one of embodiments 201-202, wherein the alkali metal alkoxide B8 is sodium ethoxide. 206. The process of embodiment 204 or 205, wherein the solvent component S17 comprises an alcohol. 207. The process of any one of embodiments 204-206, wherein the solvent component S17 comprises formula C _1-6 alkyl-OH. 208. The process of any one of embodiments 204-207, wherein the solvent component S17 comprises ethanol. 209. The process of any one of embodiments 182-193, wherein the compound of formula 27a is prepared by a process comprising: reacting a compound of formula 25P: with an alkali metal alkoxide B9 to form the compound of formula 27a. 210. The process of embodiment 209, wherein from about 1 to about 2 molar equivalents of alkali metal alkoxide B9 is utilized relative to the compound of formula 25P. 211. The process of embodiment 209, wherein about 1 molar equivalent of alkali metal alkoxide B9 is utilized relative to the compound of formula 25P. 212. The process of any one of embodiments 209-211, wherein the reacting of the compound of formula 25P with an alkali metal alkoxide B9 is carried out at a temperature of about 50 °C to about 80 °C. 213. The process of any one of embodiments 209-212, wherein the reacting of the compound of formula 25P with an alkali metal alkoxide B9 is carried out in a solvent component S18, wherein the solvent component S18 comprises formula C _1-6 alkyl- OH. 214. The process of embodiment 213, wherein the solvent component S18 comprises ethanol. 215. The process of any one of embodiments 201-214, wherein the compound of formula 25P is prepared by a process comprising: reacting a compound of formula 2P: 2P with diethyl malonate and a base B10, wherein P ¹ is an amino protecting group. 216. The process of embodiment 215, wherein the base B10 is an alkali metal carbonate. 217. The process of embodiment 215 or 216, wherein the base B10 is cesium carbonate. 218. The process of any one of embodiments 215-217, wherein the reacting of the compound of formula 2P with a base B10 is carried out at a temperature of about 40 °C to about 70 °C. 219. The process of any one of embodiments 215-218, wherein the reacting of the compound of formula 2P with a base B10 is carried out in a solvent component S19, wherein the solvent component S19 comprises a polar aprotic solvent. 220. The process of embodiment 219, wherein the solvent component S19 comprises dimethylformamide. 221. The process of any one of embodiments 215-220, wherein the compound of formula 2P is prepared by a process comprising protecting a compound of formula 12a to form the compound of formula 2P. 222. The process of embodiment 221, wherein the protecting comprise reacting the compound of formula 12a with a base B11 and P ¹ -Y, wherein Y is halo. 223. The process of embodiment 222, wherein P ¹ is p-toluenesulfonyl. 224. The process of embodiment 222 or 223, wherein the base B11 is an alkali metal hydroxide. 225. The process of any one of embodiments 222-224, wherein the base B11 is sodium hydroxide. 226. The process of any one of embodiments 222-225, wherein the protecting comprise reacting the compound of formula 12a with a base B11 is carried out in a solvent component S20, wherein the solvent component S20 comprises a polar aprotic solvent. 227. The process of embodiment 226, wherein the solvent component S20 comprises acetone. 228. The process of any one of embodiments 101-113 and 221-227 wherein the compound of formula 12a is prepared by a process comprising: reacting a compound of formula 11a: 11a or a salt thereof, with a strong acid A4. 229. The process of embodiment 228, wherein the strong acid A4 is hydrochloric acid. 230. The process of embodiment 228 or 229, wherein the reacting of the compound of formula 11a, or a salt thereof, with a strong acid A4 is carried out in a solvent component S21, wherein the solvent component S21 comprises a polar aprotic solvent. 231. The process of embodiment 230, wherein the solvent component S21 comprises a di-C _1-6 alkyl ether or a 4-10 membered heterocycloalkyl ether. 232. The process of embodiment 230 or 231, wherein the solvent component S21 comprises tetrahydrofuran. 233. The process of any one of embodiments 228-232, wherein the reacting of the compound of formula 11a, or a salt thereof, with a strong acid A4 is carried out at the refluxing temperature of tetrahydrofuran. 234. The process of any one of embodiments 228-233, wherein the compound of formula 11a, or a salt thereof, is prepared by a process comprising: reacting a compound of formula 10a: or a salt thereof, with (methoxymethyl)triphenylphosphonium chloride and a base B12. 235. The process of embodiment 234, wherein the base B12 is an alkali metal alkoxide. 236. The process of embodiment 234 or 235, wherein the base B12 is potassium t- butoxide. 237. The process of any one of embodiments 234-236, wherein the reacting of the compound of formula 11a, or a salt thereof, with (methoxymethyl)triphenylphosphonium chloride and a base B12 is carried out at a temperature of about 10 °C to about 30 °C. 238. The process of any one of embodiments 234-237, wherein the reacting of the compound of formula 11a, or a salt thereof, with (methoxymethyl)triphenylphosphonium chloride and a base B12 is carried out in a solvent component S22, wherein the solvent component S22 comprises a polar aprotic solvent. 239. The process of embodiment 238, wherein the solvent component S22 comprises a di-C _1-6 alkyl ether or a 4-10 membered heterocycloalkyl ether. 240. The process of embodiment 238 or 239, wherein the solvent component S22 comprises tetrahydrofuran. 241. The process of any one of embodiments 238-240, wherein the compound of formula 10a, or a salt thereof, is prepared by a process comprising: reacting a compound of formula 9a: with ammonia. 242. The process of embodiment 241, wherein the reacting of the compound of formula 9a with ammonia is carried out at a temperature of about 40 °C to about 70 °C. 243. The process of embodiment 241 or 242, wherein the reacting of the compound of formula 9a with ammonia is carried out in a solvent component S23, wherein the solvent component S23 comprises organic solvent. 244. The process of embodiment 243, wherein the solvent component S23 comprises toluene. 245. The process of any one of embodiments 241-244, wherein the compound of formula 9a is prepared by a process comprising: reacting a compound of formula 8a: with a Vilsmeier reagent formed from dimethylformamide. 246. The process of embodiment 245, wherein the Vilsmeier reagent is prepared by a process comprising reacting dimethylformamide with a chlorinating agent. 247. The process of embodiment 246, wherein the chlorinating agent is selected from oxalyl chloride, phosphorus oxychloride, triphosgene, thionyl chloride, sulfuryl chloride, and phosphorus pentachloride. 248. The process of embodiment 246 or 247, wherein the chlorinating agent is phosphorus oxychloride. 249. The process of any one of embodiments 101-113 and 221-237, wherein the compound of formula 12a is prepared by a process comprising: reacting a compound of formula 15a: with a chlorinating agent. 250. The process of embodiment 249, wherein the chlorinating agent is selected from oxalyl chloride, phosphorus oxychloride, triphosgene, thionyl chloride, sulfuryl chloride, and phosphorus pentachloride. 251. The process of embodiment 249 or 250, wherein the chlorinating agent is phosphorus oxychloride. 252. The process of any one of embodiments 249-251, wherein the reacting of the compound of formula 15a with a chlorinating agent is carried out at a temperature of about 50 °C to about 100 °C. 253. The process of any one of embodiments 249-252, wherein the reacting of the compound of formula 15a with ammonia is carried out in a solvent component S24, wherein the solvent component S24 comprises an organic solvent. 254. The process of embodiment 253, wherein the solvent component S24 comprises toluene. 255. The process of any one of embodiments 249-254, wherein the compound of formula 15a is prepared by a process comprising: (i) reacting a compound of formula 14a: with formamidine acetate and an alkali metal hydroxide to generate a compound of formula 14aa: ; and (ii) reacting the compound of formula 14aa with a strong acid A4. 256. The process of embodiment 255, wherein the alkali metal hydroxide is sodium ethoxide. 257. The process of embodiment 255 or 256, wherein the reacting of the compound of formula 14a with formamidine acetate and an alkali metal hydroxide is carried out at a temperature of about 50 °C to about 100 °C. 258. The process of any one of embodiments 255-257, wherein the reacting of the compound of formula 14a with formamidine acetate and an alkali metal hydroxide is carried out in a solvent component S25, wherein the solvent component S25 comprises a polar protic solvent. 259. The process of embodiment 258, wherein the solvent component S25 comprises an alcohol. 260. The process of embodiment 258 or 259, wherein the solvent component S25 comprises formula C _1-6 alkyl-OH. 261. The process of any one of embodiments 258-260, wherein the solvent component S25 comprises ethanol. 262. The process of any one of embodiments 258-261, wherein the strong acid A4 is hydrochloric acid. 263. The process of any one of embodiments 258-262, wherein the compound of formula 14a is prepared by a process comprising: reacting a compound of formula 13a: with bromoacetaldehyde diethyl acetal and sodium tert-amyloxide. 264. The process of embodiment 263, wherein the reacting of the compound of formula 13a with bromoacetaldehyde diethyl acetal and sodium tert-amyloxide is carried out at a temperature of about 80 °C to about 100 °C. 265. The process of embodiment 263 or 264, wherein the reacting of the compound of formula 13a with bromoacetaldehyde diethyl acetal and sodium tert-amyloxide is carried out in a solvent component S26, wherein the solvent component S26 comprises a polar aprotic solvent. 266. The process of embodiment 265, wherein the solvent component S26 comprises dimethylsulfoxide. 267. The process of any one of embodiments 1-266, wherein the compound of formula 3a, or the salt thereof, is the L-tartrate salt of the compound of formula 3. 268. The process of embodiment 267, wherein the L-tartrate salt of formula 3 is prepared by a process comprising: reacting compound 7a: with L-tartaric acid. 269. The process of embodiment 268, wherein about 1 molar equivalent of L- tartaric acid is utilized relative to the compound of formula 7a. 270. The process of embodiment 268 or 269, wherein the reacting of the compound of formula 7a with L-tartaric acid is carried out in a solvent component S27. 271. The process of embodiment 270, wherein the solvent component S27 comprises water and organic solvent. 272. The process of embodiment 270 or 271, wherein the solvent component S27 comprises about 1:1 (v) of water to organic solvent. 273. The process of any one of embodiments 270-272, wherein the solvent component S27 comprises a polar aprotic solvent. 274. The process of any one of embodiments 270-273, wherein the solvent component S27 comprises acetonitrile. 275. The process of any one of embodiments 268-274, wherein the reacting of the compound of formula 7a with L-tartaric acid is carried out at a temperature of from about 20 °C to about 30 °C. 276. The process of any one of embodiments 268-275, wherein the reacting of the compound of formula 7a and L-tartaric acid further comprises seeding with the salt of formula 3a. 277. The process of any one of embodiments 268-276, wherein the compound of formula 7a is prepared by a process comprising: reacting the compound of formula 6a: with hydrazine. 278. The process of embodiment 277, wherein from about 2 to about 3 equivalents of hydrazine is utilized relative to Compound 6a. 279. The process of embodiment 278, wherein the hydrazine is hydrazine hydrate. 280. The process of embodiment 278 or 279, wherein the reacting of the compound of formula 6a with hydrazine is carried out a temperature of from about -10 °C to about 30 °C. 281. The process of any one of embodiments 1-280, wherein the salt of ruxolitinib is ruxolitinib phosphate. 282. The process of embodiment 281, wherein ruxolitinib phosphate is prepared by a process comprising reacting ruxolitinib with phosphoric acid. 283. The process of embodiment 282, wherein from about 1 to about 2 molar equivalents of phosphoric acid is utilized relative to ruxolitinib. 284. The process of embodiment 282 or 283, wherein the reacting of ruxolitinib with phosphoric acid is carried out a temperature of about 20 °C to about 50 °C. 285. The process of any one of embodiments 282-284, wherein the phosphoric acid is an aqueous solution of phosphoric acid. 286. The process of any one of embodiments 281-285, wherein ruxolitinib phosphate is purified by a process comprising: (i) adding a first solvent component to ruxolitinib phosphate to generate a first solution; (ii) concentrating the first solution to generate a second solution; (iii) adding a second solvent component to the second solution to generate a third solution; (iv) adding a third solvent to the third solution to generate a fourth solution; (v) concentrating the fourth solution to generate a fifth solution; and (vi) isolating ruxolitinib phosphate from the fifth solution. 287. The process of embodiment 286, wherein the first solvent component comprises C _1-6 alkyl-OH. 288. The process of embodiment 286 or 287, wherein the first solvent component comprises methanol. 289. The process of any one of embodiments 286-288, wherein the first solution is heated to a temperature between about 30 °C to about 80 °C. 290. The process of any one of embodiments 286-289, wherein the second solvent component comprises C _1-6 alkyl-OH. 291. The process of any one of embodiments 286-290, wherein the second solvent component comprises isopropyl alcohol. 292. The process of any one of embodiments 286-291, wherein the temperature of the second solution is between about 30 °C to about 80 °C. 293. The process of any one of embodiments 286-292, wherein the third solvent component comprises a non-polar solvent. 294. The process of any one of embodiments 286-293, wherein the third solvent component comprises a C1-8 alkane. 295. The process of any one of embodiments 286-294, wherein the third solvent comprises n-heptane. 296. The process of any one of embodiments 286-295, wherein the temperature of the third solution is between about 30 °C to about 80 °C. 297. The process of any one of embodiments 286-296, wherein the fifth solution is cooled to about 20 °C to about 30 °C. 298. A process of preparing ruxolitinib phosphate, comprising: (a) reacting a compound of formula 1a, or a salt thereof: with a Vilsmeier reagent formed from dimethylformamide to generate a compound of formula 2c: (b) reacting the compound of formula 2c with a L-tartrate salt of a compound of formula 3: to provide ruxolitinib; and (c) reacting ruxolitinib with phosphoric acid to generate ruxolitinib phosphate. 299. The process of embodiment 298, wherein the compound of formula 1a or a salt thereof is prepared by a process comprising: (a) reacting a compound of formula 12a: with t-butyldimethylsilyl chloride to generate a compound of formula 12b: (b) reacting the compound of formula 12b with MeMgBr in the presence of a Grignard catalyst to generate a compound of formula 12c: and (c) deprotecting the compound of formula 12c to generate a compound of formula 1a or a salt thereof. 300. The process of embodiment 298, wherein the compound of formula 1a or a salt thereof is prepared by a process comprising: (a) reacting a compound of formula 22a: 22a with t-butyldimethylsilyl chloride and MeMgBr in the presence of a Grignard catalyst to generate a compound of formula 23a : (b) reacting the compound of formula 23a with hydrogen and palladium on carbon to generate a compound of formula 1a or a salt thereof. 301. A compound which is or a salt thereof. 302. The compound of embodiment 301, wherein the compound or a salt thereof is selected from: , and 303. A compound which is: , or a salt thereof. 304. A compound which is: or a salt thereof. 305. A compound which is: or a salt thereof. 306. A compound which is: or a salt thereof. 307. A compound which is: or a salt thereof. 308. A compound which is a salt of formula 2a: wherein X- is a counter anion other than Cl-. 309. The compound of embodiment 308, wherein the compound is selected from: (Compound 2 chloride hydrochloride), (Compound 2 perchlorate), (Compound 2 tetrafluoroborate), (Compound 2 hexfluorophosphate), (Compound 2 hexafluoroarsenate), and (Compound 2 hexafluoroantimonate). 310. A crystalline form of the salt of formula 2d: 311. The crystalline form of embodiment 310, having Form I. 312. The crystalline form of embodiment 311, having an X-ray powder diffraction (XRPD) pattern as substantially shown in Figure 1. 313. The crystalline form of embodiment 311 or 312, having a differential scanning calorimetry (DSC) thermogram substantially as depicted in Figure 2. 314. The crystalline form of any one of embodiments 311-313, having a thermogravimetric analysis (TGA) thermogram substantially as depicted in Figure 3. 315. The crystalline form of any one of embodiments 311-314, having at least one XRPD peak, in terms of 2-theta (± 0.2 degrees), selected from 7.4, 12.5, 13.1, 14.1, 14.6, 15.0, 15.9, 17.7, 18.5, 19.0, 20.5, 20.8, 22.2, 23.0, 24.3, 26.3, and 27.9 degrees. 316. The crystalline form of any one of embodiments 311-314, having at least two XRPD peaks, in terms of 2-theta (± 0.2 degrees), selected from 7.4, 12.5, 13.1, 14.1, 14.6, 15.0, 15.9, 17.7, 18.5, 19.0, 20.5, 20.8, 22.2, 23.0, 24.3, 26.3, and 27.9 degrees. 317. The crystalline form of any one of embodiments 311-314, having at least three XRPD peaks, in terms of 2-theta (± 0.2 degrees), selected from 7.4, 12.5, 13.1, 14.1, 14.6, 15.0, 15.9, 17.7, 18.5, 19.0, 20.5, 20.8, 22.2, 23.0, 24.3, 26.3, and 27.9 degrees. 318. The crystalline form of any one of embodiments 311-314, having at least four XRPD peaks, in terms of 2-theta (± 0.2 degrees), selected from 7.4, 12.5, 13.1, 14.1, 14.6, 15.0, 15.9, 17.7, 18.5, 19.0, 20.5, 20.8, 22.2, 23.0, 24.3, 26.3, and 27.9 degrees. 319. The crystalline form of any one of embodiments 311-314, having characteristic XRPD peaks, in terms of 2-theta (± 0.2 degrees), at 7.4, 12.5, 13.1, 14.1, 14.6, 15.0, 15.9, 17.7, 18.5, 19.0, 20.5, 20.8, 22.2, 23.0, 24.3, 26.3, and 27.9 degrees. 320. The crystalline form of any one of embodiments 311-319, having an endothermic peak with an onset temperature (± 3 °C) at 56 °C and a maximum at 101 °C in a DSC thermogram. 321. The crystalline form of embodiment 310, having Form II. 322. The crystalline form of embodiment 321, having an XRPD pattern as substantially shown in Figure 4. 323. The crystalline form of embodiment 321 or 322, having a DSC thermogram substantially as depicted in Figure 5. 324. The crystalline form of any one of embodiments 321-323, having a TGA thermogram substantially as depicted in Figure 6. 325. The crystalline form of any one of embodiments 321-324, having at least one XRPD peak, in terms of 2-theta (± 0.2 degrees), selected from 7.3, 11.5, 11.9, 13.3, 15.5, 15.8, 16.1, 17.4, 19.1, 19.4, 19.6, 21.4, 22.0, 22.6, 23.2, 24.9, 25.5, 26.7, and 29.1 degrees. 326. The crystalline form of any one of embodiments 321-324, having at least two XRPD peaks, in terms of 2-theta (± 0.2 degrees), selected from 7.3, 11.5, 11.9, 13.3, 15.5, 15.8, 16.1, 17.4, 19.1, 19.4, 19.6, 21.4, 22.0, 22.6, 23.2, 24.9, 25.5, 26.7, and 29.1 degrees. 327. The crystalline form of any one of embodiments 321-324, having at least three XRPD peaks, in terms of 2-theta (± 0.2 degrees), selected from 7.3, 11.5, 11.9, 13.3, 15.5, 15.8, 16.1, 17.4, 19.1, 19.4, 19.6, 21.4, 22.0, 22.6, 23.2, 24.9, 25.5, 26.7, and 29.1 degrees. 328. The crystalline form of any one of embodiments 321-324, having at least four XRPD peaks, in terms of 2-theta (± 0.2 degrees), selected from 7.3, 11.5, 11.9, 13.3, 15.5, 15.8, 16.1, 17.4, 19.1, 19.4, 19.6, 21.4, 22.0, 22.6, 23.2, 24.9, 25.5, 26.7, and 29.1 degrees. 329. The crystalline form of any one of embodiments 321-324, having characteristic XRPD peaks, in terms of 2-theta (± 0.2 degrees), at 7.3, 11.5, 11.9, 13.3, 15.5, 15.8, 16.1, 17.4, 19.1, 19.4, 19.6, 21.4, 22.0, 22.6, 23.2, 24.9, 25.5, 26.7, and 29.1 degrees. 330. The crystalline form of any one of embodiments 321-329, having an endothermic peak with an onset temperature (± 3 °C) at 47 °C and a maximum at 99 °C in a DSC thermogram. 331. A crystalline form of Compound 2 hexfluorophosphate: (Compound 2 hexfluorophosphate). 332. The crystalline form of embodiment 331, having an XRPD pattern as substantially shown in Figure 7. 333. The crystalline form of embodiment 331 or 332, having a DSC thermogram substantially as depicted in Figure 8. 334. The crystalline form of any one of embodiments 331-333, having a TGA thermogram substantially as depicted in Figure 9. 335. The crystalline form of any one of embodiments 331-334, having at least one XRPD peak, in terms of 2-theta (± 0.2 degrees), selected from 10.8, 12.0, 13.9, 14.3, 15.2, 16.6, 17.0, 17.6, 18.1, 20.1, 20.4, 21.3, 21.5, 22.1, 24.2, 24.7, 25.0, and 26.3 degrees. 336. The crystalline form of any one of embodiments 331-334, having at least two XRPD peaks, in terms of 2-theta (± 0.2 degrees), selected from 10.8, 12.0, 13.9, 14.3, 15.2, 16.6, 17.0, 17.6, 18.1, 20.1, 20.4, 21.3, 21.5, 22.1, 24.2, 24.7, 25.0, and 26.3 degrees. 337. The crystalline form of any one of embodiments 331-334, having at least three XRPD peaks, in terms of 2-theta (± 0.2 degrees), selected from 10.8, 12.0, 13.9, 14.3, 15.2, 16.6, 17.0, 17.6, 18.1, 20.1, 20.4, 21.3, 21.5, 22.1, 24.2, 24.7, 25.0, and 26.3 degrees. 338. The crystalline form of any one of embodiments 331-334, having at least four XRPD peaks, in terms of 2-theta (± 0.2 degrees), selected from 10.8, 12.0, 13.9, 14.3, 15.2, 16.6, 17.0, 17.6, 18.1, 20.1, 20.4, 21.3, 21.5, 22.1, 24.2, 24.7, 25.0, and 26.3 degrees. 339. The crystalline form of any one of embodiments 331-334, having characteristic XRPD peaks, in terms of 2-theta (± 0.2 degrees), at 10.8, 12.0, 13.9, 14.3, 15.2, 16.6, 17.0, 17.6, 18.1, 20.1, 20.4, 21.3, 21.5, 22.1, 24.2, 24.7, 25.0, and 26.3 degrees. 340. The crystalline form of any one of embodiments 331-339, having a first endothermic peak with an onset temperature (± 3 °C) at 232 °C and a maximum at 233 °C and a second endothermic peak with an onset temperature (± 3 °C) at 241 °C and a maximum at 242 °C in a DSC thermogram 341. A crystalline form of Compound 3a: 342. The crystalline form of embodiment 341, having an XRPD pattern as substantially shown in Figure 11. 343. The crystalline form of embodiment 341 or 342, having a DSC thermogram substantially as depicted in Figure 12. 344. The crystalline form of any one of embodiments 341-343, having a TGA thermogram substantially as depicted in Figure 13. 345. The crystalline form of any one of embodiments 341-344, having at least one XRPD peak, in terms of 2-theta (± 0.2 degrees), selected from 6.4, 12.8, 13.8, 16.3, 17.3, 18.0, 18.2, 19.3, 22.5, 25.9, 26.4, 27.2, and 29.6 degrees. 346. The crystalline form of any one of embodiments 341-344, having at least two XRPD peaks, in terms of 2-theta (± 0.2 degrees), selected from 6.4, 12.8, 13.8, 16.3, 17.3, 18.0, 18.2, 19.3, 22.5, 25.9, 26.4, 27.2, and 29.6 degrees. 347. The crystalline form of any one of embodiments 341-344, having at least three XRPD peaks, in terms of 2-theta (± 0.2 degrees), selected from 6.4, 12.8, 13.8, 16.3, 17.3, 18.0, 18.2, 19.3, 22.5, 25.9, 26.4, 27.2, and 29.6 degrees. 348. The crystalline form of any one of embodiments 341-344, having at least four XRPD peaks, in terms of 2-theta (± 0.2 degrees), selected from 6.4, 12.8, 13.8, 16.3, 17.3, 18.0, 18.2, 19.3, 22.5, 25.9, 26.4, 27.2, and 29.6 degrees. 349. The crystalline form of any one of embodiments 341-344, having characteristic XRPD peaks, in terms of 2-theta (± 0.2 degrees), at 6.4, 12.8, 13.8, 16.3, 17.3, 18.0, 18.2, 19.3, 22.5, 25.9, 26.4, 27.2, and 29.6 degrees. 350. The crystalline form of any one of embodiments 341-349, having a first endothermic peak with an onset temperature (± 3 °C) at 55 °C and a maximum at 79 °C and a second endothermic peak with an onset temperature (± 3 °C) at 121 °C and a maximum at 124 °C in a DSC thermogram. 351. The crystalline form of embodiment 341, characterized by single crystal x-ray diffraction having a monoclinic P21 space group and cell formula units (Z) of 4. 352. The crystalline form of embodiment 351, wherein the space group has unit cell parameters: a is about 7.68 Å, b is about 7.60 Å, c is about 13.72 Å, and beta is about 96.94°. 353. The crystalline form of any one of embodiments 341-352, wherein Compound 3a has a chiral purity of greater than 99%. Example 1. Preparation of (E)-N-(3-(Dimethylamino)-2-(7H-pyrrolo[2,3- d]pyrimidin-4-yl)allylidene)-N-methylmethanaminium chloride hydrochloride (Compound 2 chloride hydrochloride) A solution of oxalyl chloride (21.88 g, 15.1 mL, 169 mmol, 2.25 equiv) in anhydrous acetonitrile (65 mL) was cooled to 0 – 5 °C in an ice bath. Anhydrous DMF (70.8 g, 75.0 mL, 969 mmol, 12.9 equiv) was added dropwise into the solution to form the corresponding Vilsmeier reagent. During addition of DMF, the internal temperature was controlled to below 10 °C. The ice batch was removed and the reaction mixture was gradually warmed to ambient temperature over 40 minutes. Methyl-7H-pyrrolo[2,3-d]pyrimidine (1a, 10.0 g, 75.1 mmol) was charged into the in- situ generated Vilsmeier reagent as a solid in one portion at ambient temperature and the resulting slurry was agitated at ambient temperature for 5 – 10 minutes to ensure complete mixing before being warmed to 85 – 90 °C. The reaction mixture was agitated at 85 – 90 °C for one hour before being gradually cooled to ambient temperature. Anhydrous tetrahydrofuran (THF, 100 mL) was charged and the resulting slurry was agitated at ambient temperature for two hours followed by at 0 – 5 °C for two hours. The solids were collected by filtration, washed with a one to one mixture of THF and MTBE (2 x 100 mL), and dried under vacuum to constant weight to afford the desired product, (E)-N-(3-(Dimethylamino)-2-(7H-pyrrolo[2,3- d]pyrimidin-4-yl)allylidene)-N-methylmethanaminium chloride hydrochloride (2d, 24.38 g, 23.72 g theoretical, 98.9 % by HPLC area%, 90.2 wt% by NMR, 92.6% yield), as a yellow to brown crystalline solid (Form I), which contained 6 – 7% of DMF and acetonitrile and 1 – 2% of water and was used in the subsequent reaction without further purification. For Compound 2d : ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.65 (s, 1H), 8.99 (s, 1H), 8.48 (s, 2H), 7.99 – 7.94 (m, 1H), 6.84 (dd, J = 3.6, 1.6 Hz, 1H), 3.48 (s, 6H), 2.82 (s, 6H) ppm; ¹³ C NMR (DMSO-d ₆ , 125MHz) δ 163.8, 151.3, 147.6, 145.0, 132.1, 117.5, 102.9, 91.6, 48.9, 42.1 ppm; C ₁₃ H ₁₉ Cl ₂ N ₅ (MW, 279.77 for Compound 2c and 244.32 for Compound 2 without anion) LCMS (EI) m/e 244.2 (M ⁺ , base peak). Crystalline Form I of Compound 2d was characterized by XRPD, DSC and TGA. X-Ray Powder Diffraction (XRPD): The X-Ray Powder Diffraction (XRPD) was obtained from Bruker D8 Advance ECO X-ray Powder Diffractometer (XRPD) instrument. The general experimental procedures for XRPD were: (1) X-ray radiation from copper at 1.5418 Å and LYNXEYE ^TM detector; (2) X-ray power at 40 kV, 25 mA; and (3) the sample powder was dispersed on a zero-background sample holder. The general measurement conditions for XRPD were: Start Angle 3 degrees; Stop Angle 30 degrees; Sampling 0.015 degrees; and Scan speed 2 degree/min. Form I of Compound 2d was confirmed to be crystalline solid according to XRPD analysis. The XRPD pattern of Compound 2d crystalline Form I is shown in Figure 1 and the peak data is given in Table 1. Table 1. XRPD Peak Data for Compound 2d Form I Differential Scanning Calorimetry (DSC): The DSC was obtained from TA Instruments Differential Scanning Calorimetry, Discovery DSC2500 with autosampler. The DSC instrument conditions were as follows: 20-300 °C at 10 °C/min; Tzero aluminum sample pan and lid; and nitrogen gas flow at 50 mL/min. DSC analysis of Compound 2d crystalline Form I revealed one endothermic peak with an onset temperature of 55.6 °C and a maximum at 100.6 °C. The DSC thermogram of Compound 2d crystalline Form I is provided in Figure 2. Thermogravimetric Analysis (TGA): The TGA was obtained from TA Instruments Thermogravimetric Analyzer, Discovery TGA5500 with autosampler. The general experimental conditions for TGA were: ramp from 25 °C to 300 °C at 10 °C/min; nitrogen purge gas flow at 25 mL/min; platinum sample holder. TGA analysis of Compound 2d crystalline Form I revealed 8.0% weight loss below 100 °C and significant weight loss above 175 °C due to decomposition. The TGA thermogram of Compound 2d crystalline Form I is provided in Figure 3. Example 2: Alternative Preparation of (E)-N-(3-(Dimethylamino)-2-(7H- pyrrolo[2,3-d]pyrimidin-4-yl)allylidene)-N-methylmethanamini um chloride hydrochloride (Compound 2d) A solution of oxalyl chloride (43.76 g, 30.2 mL, 338 mmol, 2.25 equiv) in anhydrous acetonitrile (130 mL) was cooled to 0 – 5 °C in an ice bath. Anhydrous DMF (141.6 g, 140.0 mL, 1938 mmol, 12.9 equiv) was added dropwise into the solution to form the corresponding Vilsmeier reagent. During addition of DMF, the internal temperature was controlled to below 10 °C. The ice bath was removed and the reaction mixture was gradually warmed to ambient temperature over 40 minutes. Methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 1a hydrochloride 25.44 g, 150 mmol) was charged into the in-situ generated Vilsmeier reagent as a solid in one portion at ambient temperature and the resulting slurry was agitated at ambient temperature for 5 – 10 minutes to ensure complete mixing before being warmed to 85 – 90 °C. The reaction mixture was agitated at 85 – 90 °C for one hour before being gradually cooled to ambient temperature. Anhydrous tetrahydrofuran (THF, 200 mL) was charged and the resulting slurry was agitated at ambient temperature for 48 hours followed by at 0 – 5 °C for 2 hours. The solids were collected by filtration, washed with a one to one mixture of THF and MTBE (2 x 200 mL), and dried under vacuum to constant weight to afford the desired product, (E)-N- (3-(Dimethylamino)-2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)allyli dene)-N- methylmethanaminium chloride hydrochloride (Compound 2d), 46.17 g, 47.43 g theoretical, 99.5 % by HPLC area%, 95.2 wt% by NMR, 92.7 % yield), as a yellow to brown crystalline solid (Form II), which contained 2.3% of DMF and acetonitrile and 0.8 % of water and was used in the subsequent reaction without further purification. For Compound 2d: ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.65 (s, 1H), 8.99 (s, 1H), 8.48 (s, 2H), 7.99 – 7.94 (m, 1H), 6.84 (dd, J = 3.6, 1.6 Hz, 1H), 3.48 (s, 6H), 2.82 (s, 6H) ppm; ¹³ C NMR (DMSO-d ₆ , 125MHz) δ 163.8, 151.3, 147.6, 145.0, 132.1, 117.5, 102.9, 91.6, 48.9, 42.1 ppm; C ₁₃ H ₁₉ Cl ₂ N ₅ (MW, 279.77 for Compound 2c and 244.32 for Compound 2 without anion) LCMS (EI) m/e 244.2 (M ⁺ , base peak). Crystalline Form II of Compound 2d was characterized by XRPD, DSC and TGA. X-Ray Powder Diffraction (XRPD): The X-Ray Powder Diffraction (XRPD) was obtained from Bruker D8 Advance ECO X-ray Powder Diffractometer (XRPD) instrument. The general experimental procedures for XRPD were: (1) X-ray radiation from copper at 1.5418 Å and LYNXEYE ^TM detector; (2) X-ray power at 40 kV, 25 mA; and (3) the sample powder was dispersed on a zero-background sample holder. The general measurement conditions for XRPD were: Start Angle 3 degrees; Stop Angle 30 degrees; Sampling 0.015 degrees; and Scan speed 2 degree/min. Crystalline Form II of Compound 2d was confirmed to be crystalline solid according to XRPD analysis. The XRPD pattern of Compound 2d crystalline Form II is shown in Figure 4 and the peak data is given in Table 2. Table 2. XRPD Peak Data for Compound 2d Form II Differential Scanning Calorimetry (DSC): The DSC was obtained from TA Instruments Differential Scanning Calorimetry, Discovery DSC2500 with autosampler. The DSC instrument conditions were as follows: 20-300 °C at 10 °C/min; Tzero aluminum sample pan and lid; and nitrogen gas flow at 50 mL/min. DSC analysis of Compound 2d crystalline Form II revealed one endothermic peak with an onset temperature of 46.6 °C and a maximum at 99.2 °C. The DSC thermogram of Compound 2d crystalline Form II is provided in Figure 5. Thermogravimetric Analysis (TGA): The TGA was obtained from TA Instruments Thermogravimetric Analyzer, Discovery TGA5500 with autosampler. The general experimental conditions for TGA were: ramp from 25 °C to 300 °C at 10 °C/min; nitrogen purge gas flow at 25 mL/min; platinum sample holder. TGA analysis of Compound 2d crystalline Form II revealed 4.7% weight loss below 150 °C and significant weight loss above 175 °C due to decomposition. The TGA thermogram of Compound 2d crystalline Form II is provided in Figure 6. Example 3: Alternative Preparation of (E)-N-(3-(Dimethylamino)-2-(7H- pyrrolo[2,3-d]pyrimidin-4-yl)allylidene)-N-methylmethanamini um chloride hydrochloride (2d)

A solution of phosphorus oxochloride (POCl3, 17.25 g, 10.5 mL, 112.5 mmol, 1.5 equiv) in anhydrous acetonitrile (65 mL) was cooled to 0 – 5 °C in an ice bath. Anhydrous DMF (70.8 g, 70.0 mL, 968 mmol, 12.9 equiv) was added dropwise into the solution to form the corresponding Vilsmeier reagent. During addition of DMF, the internal temperature was controlled to below 10 °C. The ice batch was removed and the reaction mixture was gradually warmed to ambient temperature. Methyl-7H- pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 1a hydrochloride, 12.72 g, 75.0 mmol) was charged into the in-situ generated Vilsmeier reagent as a solid in one portion at ambient temperature and the resulting slurry was agitated at ambient temperature for 5 – 10 minutes to ensure complete mixing before being warmed to 75 – 80 °C. The reaction mixture was agitated at 75 – 80 °C for one hour before being gradually cooled to ambient temperature. Anhydrous tetrahydrofuran (THF, 100 mL) was charged and the resulting slurry was agitated at ambient temperature for two hours followed by at 0 – 5 °C for two hours. The solids were collected by filtration and washed with a one to one mixture of THF and MTBE (2 x 100 mL) to afford the desired product, (E)-N-(3-(Dimethylamino)-2-(7H-pyrrolo[2,3-d]pyrimidin-4- yl)allylidene)-N-methylmethanaminium chloride hydrochloride (Compound 2d, 27.83 g, 23.72 g theoretical, 96.1 % by HPLC area%, 69.0 wt% by NMR, 81.0 % yield), as a yellow to brown crystalline (Form I) solid, which contained 11.49 % of DMF and acetonitrile and 1.38 % of water and was used in the subsequent reaction without further purification. For Compound 2d : ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.65 (s, 1H), 8.99 (s, 1H), 8.48 (s, 2H), 7.99 – 7.94 (m, 1H), 6.84 (dd, J = 3.6, 1.6 Hz, 1H), 3.48 (s, 6H), 2.82 (s, 6H) ppm; ¹³ C NMR (DMSO-d ₆ , 125MHz) δ 163.8, 151.3, 147.6, 145.0, 132.1, 117.5, 102.9, 91.6, 48.9, 42.1 ppm; C ₁₃ H ₁₉ Cl2N ₅ (MW, 279.77 for Compound 2c and 244.32 for Compound 2 without anion) LCMS (EI) m/e 244.2 (M ⁺ , base peak). Example 4: Preparation of (R)-3-(4-(7H-Pyrrolo[2,3-d]pyrimidin-4-yl)-1H- pyrazol-1-yl)-3-cyclopentylpropanenitrile (Compound 1) A solution of (E)-N-(3-(dimethylamino)-2-(7H-pyrrolo[2,3-d]pyrimidin-4- yl)allylidene)-N-methylmethanaminium chloride hydrochloride (Compound 2d, 20.0 g, 55.8 mmol) in water (22.7 mL) was treated with an 50% aqueous solution of NaOH at 0 – 5 °C to pH 7 – 8. The resulting aqueous solution was added charcoal (3.6 g) and the mixture was agitated at ambient temperature for 2 – 4 hours. Charcoal was removed by filtration through a Celite bed and the wet charcoal cake was washed with water (20 mL). The resulting aqueous solution, which contained (E)-N-(3- (dimethylamino)-2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)allyliden e)-N- methylmethanaminium chloride (Compound 2c), was then treated with ethanol (160 mL) and (R)-3-cyclopentyl-3-hydrazinylpropanenitrile L-tartaric acid salt dihydrate (Compound 3a, 18.91 g, 55.8 mmol, 1.0 equiv) at ambient temperature. The resulting mixture was then agitated at ambient temperature for 12 – 24 hours. When the reaction was complete, the reaction mixture was filtered to remove the solids (L- tartaric acid). The cake was washed with ethanol (2 x 25 mL). The filtrate and the wash solution were combined and the combined solution was concentrated under the reduced pressure at 40 – 50 °C to remove most of ethanol. The residue was then added H ₂ O (70 mL) and dichloromethane (DCM, 200 mL). The two layers were separated, and the aqueous layer was extracted with DCM (80 mL). The combined organic extracts were washed with an aqueous sodium bicarbonate solution (4% of aqueous NaHCO ₃ solution, 112 mL) and water (2 x 100 mL) and the resulting solution, which contained the desired product, (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H- pyrazol-1-yl)-3-cyclopentylpropanenitrile (Compound 1), was concentrated under the reduced pressure and the residue (18.7 g, 17.1 g theoretical) was used for the subsequent phosphate salt formation reaction without further purification. Compound 1 free base obtained by the current synthetic method is identical in every comparable aspect with the compound obtained by the previously reported synthetic methods (US 8,410,265 B2). For Compound 1: ¹ H NMR (DMSO-d ₆ , 400 MHz) δ 12.10 (br. s, 1H), 8.78 (s, 1H), 8.67 (s, 1H), 8.36 (s, 1H), 7.58 (dd, 1H, J = 2.3, 3.4 Hz), 6.97 (dd, 1H, J = 1.5, 3.6 Hz), 4.50 (td, 1H, J = 9.7, 4.2 Hz), 3.26 (dd, 1H, J = 17.5, 10.2 Hz), 3.17 (dd, 1H, J = 17.2, 4.3 Hz), 2.40 (m, 1H), 1.78 (m, 1H), 1.85 - 1.10 (m, 7H) ppm; C17H ₁₈ N ₆ (MW, 306.37), LCMS (EI) m/e 307 (M ⁺ + H). Example 5: Alternative Preparation of (R)-3-(4-(7H-Pyrrolo[2,3-d]pyrimidin-4- yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile (Compound 1)

This is a general procedure for the preparation of Compound 1 using any one of Compound 2a salts (e.g., Compound 2 perchlorate, Compound 2 tetrafluoroborate, Compound 2 hexafluorophosphate, Compound 2 hexafluoroarsenate or Compound 2 hexafluoroantimonate) as starting material, wherein the scale, molarity and volumes can be adjusted proportionally accordingly. The preparation of Compound 1 using Compound 2 perchlorate as starting material is included herein as an illustrative example. To a solution of (E)-N-(3-(dimethylamino)-2-(7H-pyrrolo[2,3-d]pyrimidin-4- yl)allylidene)-N-methylmethanaminium perchlorate (Compound 2 perchlorate, 200.0 mg, 0.582 mmol) in ethanol (EtOH, 2.0 mL) was added (R)-3-cyclopentyl-3- hydrazinylpropanenitrile L-tartaric acid salt dihydrate (Compound 3a, 217.2 mg, 0.64 mmol, 1.1 equiv) at ambient temperature. The resulting reaction mixture was stirred at ambient temperature for 5 hours. When the reaction was complete, the reaction mixture was filtered to remove the solids (L-tartaric acid). The cake was washed with ethanol (2.0 mL). The filtrate and the wash solution were combined and the combined solution was concentrated under the reduced pressure at 40 – 50 °C to remove most of ethanol. The residue was then added H ₂ O (4.0 mL) and dichloromethane (DCM, 5.0 mL). The two layers were separated, and the aqueous layer was extracted with DCM (2 x 4.0 mL). The combined organic extracts were washed with brine (4.0 mL) and water (4.0 mL), dried over Na ₂ SO ₄ , and concentrated under the reduced pressure to afford the crude desired product, (R)-3-(4-(7H-Pyrrolo[2,3-d]pyrimidin-4-yl)-1H- pyrazol-1-yl)-3-cyclopentylpropanenitrile (Compound 1, 174 mg, 178.3 mg theoretical, 97.6 % yield), as a yellow oil, which is identical with the compound obtained by Example 4 and the previously reported synthetic methods (US 8,410,265 B2) in every comparable aspect and was used for the subsequent phosphate salt formation reaction without further purification. Example 6: Alternative Preparation of (R)-3-(4-(7H-Pyrrolo[2,3-d]pyrimidin-4- yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile (Compound 1). To a slurry of (E)-3-hydroxy-2-(7H-pyrrolo[2,3-d]pyrimidin-4- yl)acrylaldehyde (Compound 2b, 5.0 g, 26.4 mmol) in DMF (70.4 mL) was added (R)-3-cyclopentyl-3-hydrazinylpropanenitrile L-tartaric acid salt dihydrate (Compound 3a, 9.4 g, 27.7 mmol, 1.05 equiv). The resulting reaction mixture was stirred at ambient temperature for 22 hours. When the reaction was complete, water (80 mL) and sodium bicarbonate (NaHCO ₃ , 5.0 g, 59.5 mmol, 2.25 equiv) were added and the resulting mixture was agitated at ambient temperature for 30 minutes. The mixture was extracted with dichloromethane (DCM, 3 x 40 mL) and the combined organic extracts were washed with an aqueous sodium bicarbonate solution (20 mL) and water (2 x 20 mL). The DCM resulting solution, which contained the crude desired product, (R)-3-(4-(7H-Pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)- 3- cyclopentylpropanenitrile (Compound 1), was concentrated under the reduced pressure and the residue (7.88 g, 8.09 g theoretical) was used for the subsequent phosphate salt formation reaction without further purification. Compound 1 free base obtained by the current synthetic method is identical in every comparable aspect with the product obtained by the procedures listed under Examples 4-5 and the previously reported synthetic methods (US 8,410,265 B2). For Compound 1: ¹ H NMR (DMSO- d ₆ , 400 MHz) δ 12.10 (br. s, 1H), 8.78 (s, 1H), 8.67 (s, 1H), 8.36 (s, 1H), 7.58 (dd, 1H, J = 2.3, 3.4 Hz), 6.97 (dd, 1H, J = 1.5, 3.6 Hz), 4.50 (td, 1H, J = 9.7, 4.2 Hz), 3.26 (dd, 1H, J = 17.5, 10.2 Hz), 3.17 (dd, 1H, J = 17.2, 4.3 Hz), 2.40 (m, 1H), 1.78 (m, 1H), 1.85 - 1.10 (m, 7H) ppm; C17H ₁₈ N6 (MW, 306.37), LCMS (EI) m/e 307 (M ⁺ + H). Example 7: Preparation of (E)-N-(3-(Dimethylamino)-2-(7H-pyrrolo[2,3- d]pyrimidin-4-yl)allylidene)-N-methylmethanaminium chloride (Compound 2 chloride) Using POCl3 A solution of phosphorus oxochloride (POCl3, 23.0 g, 14.0 mL, 150 mmol, 2.0 equiv) in anhydrous acetonitrile (65 mL) was cooled to 0 – 5 °C in an ice bath. Anhydrous DMF (70.8 g, 70.0 mL, 968 mmol, 12.9 equiv) was added dropwise into the solution to form the corresponding Vilsmeier reagent. During addition of DMF, the internal temperature was controlled to below 10 °C. The ice batch was removed and the reaction mixture was gradually warmed to ambient temperature. Methyl-7H- pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 1a hydrochloride, 12.72 g, 75.0 mmol) was charged into the in-situ generated Vilsmeier reagent as a solid in one portion at ambient temperature and the resulting slurry was agitated at ambient temperature for 5 – 10 minutes to ensure complete mixing before being warmed to 75 – 80 °C. The reaction mixture was agitated at 75 – 80 °C for one hour before being gradually cooled to ambient temperature. Anhydrous tetrahydrofuran (100 mL) was charged and the resulting slurry was agitated at ambient temperature for two hours followed by at 0 – 5 °C for two hours. The solids were collected by filtration and washed with a one to one mixture of THF and MTBE (2 x 100 mL) to afford the desired product, (E)-N-(3-(Dimethylamino)-2-(7H-pyrrolo[2,3-d]pyrimidin-4- yl)allylidene)-N-methylmethanaminium chloride hydrochloride (Compound 2d), as a yellow to brown wet cake. The wet cake was then dissolved in water (120 mL), and the pH of the resulting aqueous solution was adjusted to 7 – 8 by treating with a 50% aqueous solution of sodium hydroxide (NaOH, 19.06 g) at 0 – 5 °C. The neutralized aqueous solution was then treated with charcoal (5.5 g) and agitated at ambient temperature for 12 hours. The charcoal was removed by filtration through a Celite bed and the Celite bed was washed with water (50 mL). The resulting aqueous solution, which contained the desired product, (E)-N-(3-(Dimethylamino)-2-(7H-pyrrolo[2,3- d]pyrimidin-4-yl)allylidene)-N-methylmethanaminium chloride (Compound 2c, > 99.0 % pure by HPLC area%), was used for the subsequent reactions without further treatment. Example 8: Synthesis of (E)-N-(3-(Dimethylamino)-2-(7H-pyrrolo[2,3- d]pyrimidin-4-yl)allylidene)-N-methylmethanaminium chloride (Compound 2c) Using Triphosgene A solution of triphosgene ((CCl3O)2CO, 37.4 g, 126 mmol, 1.5 equiv) in anhydrous acetonitrile (73 mL) was cooled to 0 – 5 °C in an ice bath. Anhydrous DMF (79.0 g, 84 mL, 1083 mmol, 12.9 equiv) was added dropwise into the solution to form the corresponding Vilsmeier reagent. During addition of DMF, the internal temperature was controlled to below 10 °C. The ice batch was removed and the reaction mixture was gradually warmed to ambient temperature over 40 minutes. Methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 1a hydrochloride, 14.25 g, 84.0 mmol) was charged into the in-situ generated Vilsmeier reagent as a solid in one portion at ambient temperature and the resulting slurry was agitated at ambient temperature for 5 – 10 minutes to ensure complete mixing before being warmed to 80 – 90 °C. The reaction mixture was agitated at 80 – 90 °C for one hour before being gradually cooled to ambient temperature. Anhydrous tetrahydrofuran (THF, 112 mL) was charged and the resulting slurry was agitated at ambient temperature for 12 hours followed by at 0 – 5 °C for 2 hours. The solids were collected by filtration, washed with a one to one mixture of THF and MTBE (2 x 200 mL), and dried under vacuum to constant weight to afford the desired product, (E)-N- (3-(Dimethylamino)-2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)allyli dene)-N- methylmethanaminium chloride (Compound 2c), 28.3 g, 23.5 g theoretical, 98.8 % by HPLC area%, 64.9 wt% by HPLC, 78.2% yield), as a yellow to brown amorphous solid, which contained 19.7 % of DMF and 0.8% of water and was used in the subsequent reaction without further purification. For Compound 2c : ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.65 (s, 1H), 8.99 (s, 1H), 8.48 (s, 2H), 7.99 – 7.94 (m, 1H), 6.84 (dd, J = 3.6, 1.6 Hz, 1H), 3.48 (s, 6H), 2.82 (s, 6H) ppm; ¹³ C NMR (DMSO-d ₆ , 125MHz) δ 163.8, 151.3, 147.6, 145.0, 132.1, 117.5, 102.9, 91.6, 48.9, 42.1 ppm; C ₁₃ H ₁₉ Cl ₂ N ₅ (MW, 279.77 for Compound 2c and 244.32 for Compound 2 without anion) LCMS (EI) m/e 244.2 (M ⁺ , base peak). Example 9: Preparation of (E)-N-(3-(dimethylamino)-2-(7H-pyrrolo[2,3- d]pyrimidin-4-yl)allylidene)-N-methylmethanaminium salts (E)-N-(3-(dimethylamino)-2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl) allylidene)-N- methylmethanaminium perchlorate (Compound 2 perchlorate): To a solution of (E)-N-(3-(dimethylamino)-2-(7H-pyrrolo[2,3-d]pyrimidin-4- yl)allylidene)-N-methylmethanaminium chloride (Compound 2c2.94 g, 10.525 mmol) in water (8.06 mL) was added sodium perchlorate (NaClO ₄ , 1.933 g, 15.79 mmol, 1.50 equiv) at ambient temperature. After stirred at 20 - 25 °C for 12 hour, the slurry was cooled in an ice bath for 2 hours. The solids was filtered, washed with cold H ₂ O (3 x 2 mL) and dried under vacuum to afford the crude desired product, (E)-N-(3- (dimethylamino)-2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)allyliden e)-N- methylmethanaminium perchlorate (Compound 2 perchlorate), as white solids, which were used in the subsequent reaction without further purification. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.50 – 12.17 (s, 1H), 8.94 – 8.73 (s, 1H), 8.08 – 7.87 (s, 2H), 7.77 – 7.57 (dd, J = 3.4, 2.3 Hz, 1H), 6.56 – 6.31 (dd, J = 3.5, 1.7 Hz, 1H), 3.54 – 3.04 (s, 6H), 2.45 – 2.17 (s, 6H) ppm; C ₁₃ H ₁₈ ClN ₅ O ₄ (MW, 343.77 for Compound 2 perchlorate and 244.32 for Compound 2 without anion) LCMS (EI) m/e 244.2 (M ⁺ , base peak). (E)-N-(3-(dimethylamino)-2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl) allylidene)-N- methylmethanaminium tetrafluoroborate (Compound 2 tetrafluoroborate): To a solution of (E)-N-(3-(dimethylamino)-2-(7H-pyrrolo[2,3-d]pyrimidin-4- yl)allylidene)-N-methylmethanaminium chloride (Compound 2c, 2.94 g, 10.525 mmol) in water (8.06 mL) was added sodium tetrafluoroborate (NaBF ₄ , 1.733 g, 15.79 mmol, 1.50 equiv) at ambient temperature. After stirring at 20 - 25 °C for 12 hours, the slurry was cooled in an ice bath for 2 hours. The solids was filtered, washed with cold H ₂ O (3 x 2 mL) and dried under vacuum to afford the crude desired product, (E)-N-(3-(dimethylamino)-2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl) allylidene)- N-methylmethanaminium tertafluoroborate (Compound 2 tetrafluoroborate, 1.80 g, 3.49 g theoretical, 51.6% yield), as a white solid, which was used in the subsequent reaction without further purification. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.39 – 12.34 (s, 1H), 8.85 – 8.80 (s, 1H), 7.99 – 7.94 (s, 2H), 7.71 – 7.65 (dd, J = 3.4, 2.2 Hz, 1H), 6.52 – 6.46 (dd, J = 3.5, 1.7 Hz, 1H), 3.34 – 3.29 (s, 6H), 2.38 – 2.33 (s, 6H) ppm; ¹¹ B NMR (DMSO-d ₆ , 128 MHz) δ – 1.27 ppm; ¹⁹ F NMR (DMSO-d ₆ , 376.5 MHz) δ – 148.23 and – 148.28 ppm; C ₁₃ H ₁₈ BF ₄ N ₅ (MW, 331.13 for Compound 2 tetrafluoroborate and 244.32 for Compound 2 without anion) LCMS (EI) m/e 244.2 (M ⁺ , base peak). (E)-N-(3-(dimethylamino)-2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl) allylidene)-N- methylmethanaminium hexafluorophosphate (Compound 2 hexafluorophosphate): To a solution of crude (E)-N-(3-(dimethylamino)-2-(7H-pyrrolo[2,3- d]pyrimidin-4-yl)allylidene)-N-methylmethanaminium chloride hydrochloride (Compound 2d, 25.61 g, 91.6 mmol) in water (80 mL), generated from 4-methyl-7H- pyrrolo[2,3-d]pyrimidine (12.19 g, 91.6 mmol) via the corresponding Vilsmeier reaction as described in Example 1, was added an aqueous solution of sodium hydroxide (NaOH) at 0 – 5 °C to adjust the solution pH to 7 – 8. The resulting aqueous solution was added charcoal (7.69 g) and the mixture was agitated at ambient temperature for 2 – 4 hours. Charcoal was removed by filtration through a Celite bed and the wet charcoal cake was washed with water (15 mL). The combined aqueous solution was then added sodium hexafluorophosphate (NaPF ₆ , 20.08 g, 120 mmol, 1.31 equiv) at ambient temperature. After stirring at 20 - 25 °C for 1 hour, the slurry was cooled in an ice bath for 30 minutes. The solids was filtered, washed with cold H ₂ O (2 x 25 mL) and dried under vacuum to afford the crude desired product, (E)-N- (3-(dimethylamino)-2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)allyli dene)-N- methylmethanaminium hexafluorophosphate (Compound 2 hexafluorophosphate, 24.30 g, 35.81 g theoretical, 67.9% yield, 98.7% by HPLC area%), as white crystalline solids, which were used in the subsequent reaction without further purification. The crude Compound 2 hexafluorophosphate can be purified by recrystallization from water to generate pure product as white crystalline solids. For Compound 2 hexafluorophosphate: ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 12.36 (s, 1H), 8.83 (s, 1H), 7.97 (br s, 2H), 7.68 (dd, J = 3.2, 2.6 Hz, 1H), 6.48 (dd, J = 3.4, 1.8 Hz, 1H), 3.32 (s, 6H), 2.36 (br s, 6H) ppm; ¹³ C NMR (125 MHz, DMSO-d ₆ ) δ 163.7, 152.9, 151.4, 151.0, 128.9, 120.7, 101.5, 99.8, 48.9, 40.0 ppm; ¹⁹ F NMR (DMSO-d ₆ , 470.6 MHz) δ – 70.2 (d, ¹ J(PF) = 711.1 Hz) ppm; ³¹ P NMR (DMSO-d ₆ , 162 MHz) δ – 144.19 (septet, ¹ J(PF) = 711 Hz) ppm. C ₁₃ H ₁₈ F ₆ N ₅ P (MW, 389.29 for Compound 2 hexafluorophosphate and 244.32 for Compound 2 without anion) LCMS (EI) m/e 244.2 (M ⁺ , base peak). The crystallinity of Compound 2 hexafluorophosphate was characterized by XRPD, DSC and TGA. X-Ray Powder Diffraction (XRPD): The X-Ray Powder Diffraction (XRPD) was obtained from Bruker D8 Advance ECO X-ray Powder Diffractometer (XRPD) instrument. The general experimental procedures for XRPD were: (1) X-ray radiation from copper at 1.5418 Å and LYNXEYE ^TM detector; (2) X-ray power at 40 kV, 25 mA; and (3) the sample powder was dispersed on a zero-background sample holder. The general measurement conditions for XRPD were: Start Angle 3 degrees; Stop Angle 30 degrees; Sampling 0.015 degrees; and Scan speed 2 degree/min. Compound 2 hexafluorophosphate was confirmed to be crystalline solid according to XRPD analysis. The XRPD pattern of Compound 2 hexafluorophosphate is shown in Figure 7 and the peak data is given in Table 3. Table 3. XRPD Peak Data for Compound 2 hexafluorophosphate Differential Scanning Calorimetry (DSC): The DSC was obtained from TA Instruments Differential Scanning Calorimetry, Discovery DSC2500 with autosampler. The DSC instrument conditions were as follows: 20-300 °C at 10 °C/min; Tzero aluminum sample pan and lid; and nitrogen gas flow at 50 mL/min. DSC analysis of Compound 2 hexafluorophosphate crystalline sample revealed one endothermic peak with an onset temperature of 231.7 °C and a maximum at 232.7 °C due to melting and second endothermic peak with an onset temperature of 241.1 °C and a maximum at 242.1 °C due to decomposition. The DSC thermogram of Compound 2 hexafluorophosphate is provided in Figure 8. Thermogravimetric Analysis (TGA): The TGA was obtained from TA Instruments Thermogravimetric Analyzer, Discovery TGA5500 with autosampler. The general experimental conditions for TGA were: ramp from 25 °C to 300 °C at 10 °C/min; nitrogen purge gas flow at 25 mL/min; platinum sample holder. TGA analysis of Compound 2 hexafluorophosphate crystalline sample revealed significant weight loss above 250 °C due to decomposition. The TGA thermogram of Compound 2 hexafluorophosphate is provided in Figure 9. (E)-N-(3-(dimethylamino)-2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl) allylidene)-N- methylmethanaminium hexafluoroarsenate (Compound 2 hexafluoroarsenate): To a solution of (E)-N-(3-(dimethylamino)-2-(7H-pyrrolo[2,3-d]pyrimidin-4- yl)allylidene)-N-methylmethanaminium chloride (Compound 2c, 2.94 g, 10.525 mmol) in water (8.06 mL) was added sodium hexafluoroarsenate (NaAsF ₆ , 3.35 g, 15.79 mmol, 1.50 equiv) at ambient temperature. After stirred at 20 - 25 °C for 12 hour, the slurry was cooled in an ice bath for 2 hours. The solids was filtered, washed with cold H ₂ O (3 x 2 mL) and dried under vacuum to afford the crude desired product, (E)-N-(3-(dimethylamino)-2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl) allylidene)- N-methylmethanaminium hexafluoroarsenate (Compound 2 hexafluoroarsenate, 4.51 g, 4.56 g theoretical, 99% yield), as white solids, which were used in the subsequent reaction without further purification. For Compound 2 hexafluoroarsenate: ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.38 (s, 1H), 8.83 (s, 1H), 7.97 (s, 2H), 7.76 - 7.57 (t, J = 2.9 Hz, 1H), 6.59 – 6.36 (dd, J = 3.2, 1.8 Hz, 1H), 3.32 (s, 6H), 2.35 (s, 6H) ppm; ¹⁹ F NMR (DMSO-d ₆ , 376.5 MHz) δ – 62.16 (quartet, ¹ J(AsF) = 937.5 Hz) ppm; C ₁₃ H ₁₈ F ₆ N ₅ As (MW, 433.23 for Compound 2 hexafluoroarsenate and 244.32 for Compound 2 without anion) LCMS (EI) m/e 244.2 (M ⁺ , base peak). (E)-N-(3-(dimethylamino)-2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl) allylidene)-N- methylmethanaminium hexafluoroantimonate (Compound 2 hexafluoroantimonate): To a solution of (E)-N-(3-(dimethylamino)-2-(7H-pyrrolo[2,3-d]pyrimidin-4- yl)allylidene)-N-methylmethanaminium chloride (Compound 2c , 2.94 g, 10.525 mmol) in water (8.06 mL) was added sodium hexafluoroantimonate (NaSbF ₆ , 4.08 g, 15.79 mmol, 1.50 equiv) at ambient temperature. After stirred at 20 - 25 °C for 12 hour, the slurry was cooled in an ice bath for 2 hours. The solids was filtered, washed with cold H ₂ O (3 x 2 mL) and dried under vacuum to afford the crude desired product, (E)-N-(3-(dimethylamino)-2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl) allylidene)- N-methylmethanaminium hexafluoroantimonate (Compound 2 hexafluoroantimonate, 2.61 g, 5.05 g theoretical, 51.7% yield), as white solids, which were used in the subsequent reaction without further purification. For Compound 2 hexafluoroantimonate: ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.37 (s, 1H), 8.83 (s, 1H), 7.98 (s, 2H), 7.68 (s, 1H), 6.49 (s, 1H), 3.32 (s, 6H), 2.35 (s, 6H) ppm; ¹⁹ F NMR (DMSO-d ₆ , 376.5 MHz) δ – 166.86 ppm; C ₁₃ H ₁₈ F ₆ N ₅ Sb (MW, 480.07 for Compound 2 hexafluoroantimonate and 244.32 for Compound 2 without anion ) LCMS (EI) m/e 244.2 (M ⁺ , base peak). Example 10: Alternative Preparation of (E)-N-(3-(dimethylamino)-2-(7H- pyrrolo[2,3-d]pyrimidin-4-yl)allylidene)-N-methylmethanamini um perchlorate (Compound 2 perchlorate) Method 1 Oxalyl chloride (20.0 mL, 228 mmol, 3.04 equiv) was slowly charged to DMF (107 mL, 1378 mmol, 18.4 equiv) over 15 minutes while keeping the internal temperature at below 50 °C. After addition, the resulting slurry was cooled to ambient temperature and stirred at ambient temperature for 2 hours.4-Methyl-7H-pyrrolo[2,3- d]pyrimidine (Compound 1a, 10.0 g, 75 mmol) was added to the slurry at ambient temperature and the resulting reaction mixture was stirred at ambient temperature for 16 hours and then at 50 °C for 5.5 hours. The reaction mixture was cooled to ambient temperature and quenched with ice (60 g). The quenched reaction mixture was concentrated under vacuum to a residue, which was then dissolved in water (50 mL). Sodium perchlorate (NaClO ₄ , 20.23 g, 165 mmol, 2.2 equiv) was then added to the aqueous solution at ambient temperature. The resulting mixture was cooled in an ice bath before sodium hydroxide (NaOH, 7.5 g, 188 mmol, 2.5 equiv) was added slowly. The solids were collected by filtration, washed with water (30 mL), and dried under vacuum to give the crude desired product, (E)-N-(3-(dimethylamino)-2-(7H- pyrrolo[2,3-d]pyrimidin-4-yl)allylidene)-N-methylmethanamini um perchlorate (Compound 2 perchlorate, 18.7 g, 25.78 g theoretical, 72.5% yield), as grey solids, which were used for the subsequent reaction without further purification. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.50 – 12.17 (s, 1H), 8.94 – 8.73 (s, 1H), 8.08 – 7.87 (s, 2H), 7.77 – 7.57 (dd, J = 3.4, 2.3 Hz, 1H), 6.56 – 6.31 (dd, J = 3.5, 1.7 Hz, 1H), 3.54 – 3.04 (s, 6H), 2.45 – 2.17 (s, 6H) ppm; C ₁₃ H ₁₈ ClN ₅ O ₄ (MW, 343.77 for Compound 2 perchlorate and 244.32 for Compound 2 without anion) LCMS (EI) m/e 244.2 (M ⁺ , base peak). Method 2 To a solution of 2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)acetic acid (Compound 5a, 354 mg, 2.0 mmol) in anhydrous DMF (2.92 g, 3.1 mL, 40 mmol, 20 equiv) was added phosphorus oxychloride (POCl3, 920 mg, 0.56 mL, 6.0 mmol, 3.0 equiv) at ambient temperature. The resulting reaction mixture was then warmed to 80 – 90 °C and agitated at 80 – 90 °C for 30 minutes. When the reaction was complete, the reaction mixture was cooled down to ambient temperature. The cooled reaction mixture was quenched by pouring into ice (10 g). The solution was then concentrated under reduced pressure and the resulting residue was treated with water (3 mL). The aqueous solution was neutralized with an aqueous solution of NaOH to pH 7 – 8 before being treated with activated charcoal (50 mg). The mixture was agitated at ambient temperature for 30 minutes before being filtered through a Celite bed. The Celite bed was washed with water (2 mL). The combined filtrate and the wash solution was then treated with solid sodium perchlorate (NaClO ₄ , 367 mg, 3.0 mmol, 1.5 equiv) at ambient temperature. The mixture was stirred at ambient temperature for 1 hour followed by at 0 – 5 °C for 1 hour. The solids were then collected by filtration, washed with water (2 x 2 mL), dried under vacuum to give the crude desired product, (E)-N-(3-(dimethylamino)-2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl) allylidene)-N- methylmethanaminium perchlorate (Compound 2 perchlorate), 330 mg, 688 mg theoretical, 48 % yield), as grey solids, which were used for the subsequent reaction without further purification. For Compound 2 perchlorate: ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.50 – 12.17 (s, 1H), 8.94 – 8.73 (s, 1H), 8.08 – 7.87 (s, 2H), 7.77 – 7.57 (dd, J = 3.4, 2.3 Hz, 1H), 6.56 – 6.31 (dd, J = 3.5, 1.7 Hz, 1H), 3.54 – 3.04 (s, 6H), 2.45 – 2.17 (s, 6H) ppm; C ₁₃ H ₁₈ ClN ₅ O ₄ (MW, 343.77 for Compound 2 perchlorate and 244.32 for Comopund 2 without anion) LCMS (EI) m/e 244.2 (M ⁺ , base peak). Method 3 To a solution of sodium 2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)acetate (Compound 5b, 1.70 g, 8.54 mmol) in anhydrous DMF (12.48 g, 13.2 mL, 171 mmol, 20 equiv) was added phosphorus oxychloride (POCl3, 3.93 g, 2.4 mL, 25.6 mmol, 3.0 equiv) at ambient temperature. The resulting reaction mixture was then warmed to 80 – 90 °C and agitated at 80 – 90 °C for 30 minutes. When the reaction was complete, the reaction mixture was cooled down to ambient temperature. The cooled reaction mixture was quenched by pouring into ice (40 g). The solution was then concentrated under reduced pressure and the resulting residue was treated with water (10 mL). The aqueous solution was neutralized with an aqueous solution of NaOH to pH 7 – 8 before being treated with activated charcoal (200 mg). The mixture was agitated at ambient temperature for 30 minutes before being filtered through a Celite bed. The Celite bed was washed with water (5 mL). The combined filtrate and the wash solution was then treated with solid sodium perchlorate (NaClO ₄ , 1.57 g, 12.8 mmol, 1.5 equiv) at ambient temperature. The mixture was stirred at ambient temperature for 1 hour followed by at 0 – 5 °C for 1 hour. The solids were then collected by filtration, washed with water (2 x 5 mL), dried under vacuum to give the desired product, (E)-N- (3-(dimethylamino)-2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)allyli dene)-N- methylmethanaminium perchlorate (Compound 2 perchlorate, 1.3 g, 2.94 g theoretical, 44.3 % yield), as off-white solids, which were used for the subsequent reaction without further purification. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.50 – 12.17 (s, 1H), 8.94 – 8.73 (s, 1H), 8.08 – 7.87 (s, 2H), 7.77 – 7.57 (dd, J = 3.4, 2.3 Hz, 1H), 6.56 – 6.31 (dd, J = 3.5, 1.7 Hz, 1H), 3.54 – 3.04 (s, 6H), 2.45 – 2.17 (s, 6H) ppm; C ₁₃ H ₁₈ ClN ₅ O ₄ (MW, 343.77 for Compound 2 perchlorate and 244.32 for Compound 2 without an anion) LCMS (EI) m/e 244.2 (M ⁺ , base peak). Example 11: Preparation of 2-(7H-Pyrrolo[2,3-d]pyrimidin-4-yl)malonaldehyde ((E)-3-hydroxy-2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)acrylaldeh yde (Compound 2b) Oxalyl chloride (12.00 ml, 137 mmol, 3.64 equiv) was added dropwise to DMF (50 mL, 646 mmol, 17.18 equiv) while keeping the internal temperature at below 50 °C. The resulting mixture was stirred at ambient temperature for 30 minutes. 4-Methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 1a, 5.00 g, 37.6 mmol) was added as a solid in one portion and the resulting reaction mixture was stirred at room temperature for 3 days and 50 °C for 4 hours. Once the reaction was complete, the reaction mixture was cooled to room temperature and quenched with ice (30 g). Sodium hydroxide (NaOH, 16.1 g, 403 mmol, 10.72 equiv) was added to the quenched reaction mixture and the mixture was stirred at room temperature for 26 hours. Additional sodium hydroxide (NaOH, 2.2 g, 55.0 mmol, 1.46 equiv) was added and the mixture was stirred at 40 °C for 4 hours. Once the hydrolysis reaction was complete, the mixture was cooled to 0 – 5 °C in an ice batch before the concentrated HCl solution was added to adjust pH to 5 - 6. The mixture was gradually warmed to ambient temperature and agitated at ambient temperature for 2 hours. Solids were collected by filtration, washed with cold water, and dried under vacuum to give the crude desired product, 2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)malonaldehyde ((E)-3- hydroxy-2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)acrylaldehyde, (Compound 2b, 6.33 g, 7.113 g theoretical, 89% yield), as a grey powder, which was used directly in the subsequent reaction without further purification. For Compound 2b: ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 13.74 (br s, 2H), 9.52 (s, 2H), 8.73 (s, 1H), 7.53 (dd, J = 3.4, 2.3 Hz, 1H), 7.46 (dd, J = 3.5, 1.7 Hz, 1H) ppm; C ₉ H ₇ N ₃ O ₂ (MW, 189.17) LCMS (EI) m/e 190.1 (M ⁺ , base peak). Example 12. Preparation of (R)-3-Cyclopentyl-3-hydrazineylpropanenitrile L- Tartrate Dihydrate (Compound 3a)

Step 1: 3-Cyclopentyl-3-hydrazineylpropanenitrile (Compound 7a): A 20 L reaction vessel was charged (E)-3-cyclopentylacrylonitrile (Compound 6a, 1040 g, 8.582 mol, 1.0 equiv), and was cooled by ice bath under nitrogen atmosphere. Hydrazine hydrate (902 g, 18.0 mol, 2.1 equiv) was slowly addded into the reaction vessle over 40 minuests with the reaction temperature controlled between 0 °C to 5 °C. The reaction mixture was then stirred at ambient temperature at 18 °C to 22 °C for 24 – 30 hours. Upon reaction completion, the reaction mixture was diluted by DCM (2080 mL) and Brine (1040 mL). The resulting biphase mixture was stirred for 10 minutes to ensure mixing. Then the organic layer was seperated and collected. The aqueous layer was extracted one more time by DCM (1040 mL). The combined organic layer was evaporated in vacuo. The crude desired product, 3-cyclopentyl-3- hydrazineylpropanenitrile (Compound 7a), was obtained as a light yellow gel, which was directly used in the next step without further purification. For Compound 7a: ¹ H NMR (DMSO-d ₆ , 400 MHz) δ 3.45 (br, 3H), 2.79 (dd, J = 16.8, 4.6 Hz, 1H), 2.56 (dd, J = 16.8, 4.6 Hz, 1H), 2.49 (dt, J = 8.9, 4.5 Hz, 1H), 1.94 – 1.65 (m, 3H), 1.62 – 1.44 (m, 4H), 1.21 (dtt, J = 20.6, 8.3, 4.6 Hz, 2H) ppm; ¹³ C NMR (DMSO-d ₆ , 101 MHz) δ ^119.90, 64.03, 42.22, 29.71 (29.75, 29.67), 25.36 (25.43, 25.29), 20.04 ppm; C ₈ H ₁₅ N3 (MW, 153.23), LCMS (EI) m/e 154.2 (M ⁺ + H). Step 2. (R)-3-Cyclopentyl-3-hydrazineylpropanenitrile (2R,3R)-2,3- dihydroxysuccinate dihydrate (Compound 3a): To a solution of L-tartaric acid (1417 g, 9.44 mol, 1.1 equiv) in one to one (volume to volume) mixture of water and acetonitrile (9.86 L) was slowly added a solution of crude 3-cyclopentyl-3-hydrazineylpropanenitrile (Compound 7a, 1315 g, 8.582 mol, 1.0 equiv) in one to one (volume to volume) mixture of water and acetonitrile (3.29 L) in 1 – 1.5 hours. The reaction mixture was protected under nitrogen with reaction temperature controlled under 25 °C by a water bath. When 42 - 43% of the 3-cyclopentyl-3-hydrazineylpropanenitrile (Compound 7a) solution was added, the reaction was seeded by the desired (R)-3-cyclopentyl-3- hydrazineylpropanenitrile (2R,3R)-2,3-dihydroxysuccinate dihydrate (Compound 3a, 0.03 – 0.05% by weight) solids. After seeding, the reaction was agitated for 10 minutes to ensure the seeds are not dissolved. Then, the rest portion of the 3- cyclopentyl-3-hydrazineylpropanenitrile (Compound 7a) solution was slowly added to the reaction mixture within 0.5 – 1 hour. The resulting reaction mixture was allowed to stir at ambient temperature for 2 hours before being slowly coold to - 2 °C – 2 °C over a 2 hour period. After stirring at - 2 °C – 2 °C for an additional 2 hours, the solids were isolated. The wet solid cake was washed three times by a 5% v/v of water in acetonitrile (2 L each time) mixture solvent. After drying the solids by pulling air through for 24 hours, the desired product, (R)-3-cyclopentyl-3- hydrazineylpropanenitrile (2R,3R)-2,3-dihydroxysuccinate dihydrate (Compound 3a), was obtained as white crystalline solids (1177 g, 40.4% over two steps). ¹ H NMR (D2O, 400 MHz) δ 4.79 (br, 11H), 4.54 (s, 2H), 3.26 (dt, J = 9.1, 4.5 Hz, 1H), 3.11 – 2.87 (m, 2H), 2.12 (h, J = 9.2 Hz, 1H), 1.92 – 1.88 (m, 2H), 1.71 – 1.62(m, 4H), 1.38 – 1.25 (m, 2H) ppm; ¹³ C NMR (D2O, 101 MHz) δ 176.36, 118.37, 72.82, 60.15, 41.01, 29.06 (29.11, 29.01), 24.69 (24.85, 24.53), 19.31 ppm; C12H25N3O8 (MW, 339.35), C ₈ H ₁₅ N ₃ (153.23, MW for free base), LCMS (EI) m/e 154.2 (M ⁺ + H); chiral purity (er, R : S) = 99.71 : 0.29; KF = 9.98; salt ratio = 1 (acid : base = 1 : 1). Optional reslurry purification of Compound 3a to improve chiral purity: To a reaction vessel was added (R)-3-cyclopentyl-3-hydrazineylpropanenitrile (2R,3R)-2,3-dihydroxysuccinate dihydrate (Compound 3a, 20 g, 1.0 equiv) and a 10% aqueous acetonitrile (water to acetonitrile = 1 : 9 by volume, 200 mL). The reaction mixture was agitated at ambient tempertature. After 16 hours, the reaction mixture was filtrated and the solid was colloected. The wet solid cake was washed twice by a 5% aqueous acetonitrile (water to acetonitrile = 5 : 95 by volume, 40 mL each time). The solid was dried by pulling air through for 24 hours, and the purified product, (R)- 3-cyclopentyl-3-hydrazineylpropanenitrile (2R,3R)-2,3-dihydroxysuccinate dihydrate (Compound 3a), was obtained as white crystalline solids. The structure and the absolute stereochemistry of Compound 3a was also confirmed by the single crystal x- ray crystallography (Figures 10A and 10B). Single crystal x-ray data: C6 H12.50 N1.50 O4 , from water, colorless, rectangular plate, ~0.240 x 0.180 x 0.020mm, monoclinic , P21 , a = 7.6791(5) Å, b = 7.5988(5) Å, c = 13.7174(8) Å, beta = 96.941(2) °, Vol = 794.57(9) Å ³ , Z = 4 , T = - 173.°C, Formula weight = 169.67, Density = 1.418g/cm ³ , µ(Cu) = 1.02mm ^-1 . The single crystal x-ray data collection: Bruker D8 Venture with PhotonII Detector, Cu Microsource, wavelength = 1.5418, anode power = 50.0kV x 1.1mA, crystal to plate distance = 2.7cm, 768 x 1024 pixels/frame, beam center = (381.11,510.89), total frames = 5679, oscillation/frame = 0.00°, exposure/frame = variable, SAINT integration, hkl min/max = ( -9 , 9 , -9 , 8 , -16 , 16 ), data input to shelx = 19514 , unique data = 3003 , two-theta range = 6.49 to 144.58°, completeness to two-theta 144.58 = 99.80%, R(int-xl) = 0.0416, SADABS correction applied. Solution and refinement: Structure solved using XS(Shelxtl), refined using shelxtl software package, refinement by full-matrix least squares on F ² , scattering factors from Int. Tab. Vol C Tables 4.2.6.8 and 6.1.1.4, number of data = 3003 , number of restraints = 1 , number of parameters = 308 , data/parameter ratio = 9.75, goodness-of-fit on F ² = 1.06, R indices[I>4sigma(I)] R1 = 0.0245, wR2 = 0.0586, R indices(all data) R1 = 0.0256, wR2 = 0.0592, max difference peak and hole = 0.250 and -0.137 e/Å ³ , refined flack parameter = 0.08(5) , All of the hydrogen atoms ehave been idealized using a riding model. The single crystal x-ray study determines that the asymmetric unit contains one C8N3H16 molecule[+1], one L-tartrate[-1], and two water molecules as shown in Figures 10A and 10B with thermal ellipsoids drawn to the 50% probability level. The predicted structure is confirmed. The enantiomeric setting was based on the chirality of the L-tartrate and the Flack parameter that refined to 0.08(5). This study determined the absolute configuration at the chiral center C1=R. The crystallinity of (R)-3-cyclopentyl-3-hydrazineylpropanenitrile L-tartrate dihydrate (Compound 3a) was characterized by XRPD, DSC and TGA. X-Ray Powder Diffraction (XRPD): The X-Ray Powder Diffraction (XRPD) was obtained from Bruker D8 Advance ECO X-ray Powder Diffractometer (XRPD) instrument. The general experimental procedures for XRPD were: (1) X-ray radiation from copper at 1.5418 Å and LYNXEYE ^TM detector; (2) X-ray power at 40 kV, 25 mA; and (3) the sample powder was dispersed on a zero-background sample holder. The general measurement conditions for XRPD were: Start Angle 3 degrees; Stop Angle 30 degrees; Sampling 0.015 degrees; and Scan speed 2 degree/min. (R)-3-cyclopentyl-3-hydrazineylpropanenitrile L-tartrate dihydrate (Compound 3a) obtained by the method described above was confirmed to be crystalline solid according to XRPD analysis. The XRPD pattern of (R)-3- cyclopentyl-3-hydrazineylpropanenitrileL-tartrate dihydrate (Compound 3a) crystalline sample is shown in Figure 11 and the peak data is given in Table 4. Table 4. XRPD Peak Data for (R)-3-Cyclopentyl-3 hydrazineylpropanenitrile L- Tartrate Dihydrate (Compound 3a) Differential Scanning Calorimetry (DSC): The DSC was obtained from TA Instruments Differential Scanning Calorimetry, Discovery DSC2500 with autosampler. The DSC instrument conditions were as follows: 20-300 °C at 10 °C/min; Tzero aluminum sample pan and lid; and nitrogen gas flow at 50 mL/min. DSC analysis of (R)-3-cyclopentyl-3-hydrazineylpropanenitrile L-tartrate dihydrate (Compound 3a) revealed one endothermic peak with an onset temperature of 55.3 °C and a maximum at 79.1 °C due to dehydration and second exothermic peak with an onset temperature of 121.0 °C and a maximum at 123.5 °C. The DSC thermogram of Compound 3a crystalline sample is provided in Figure 12. Thermogravimetric Analysis (TGA): The TGA was obtained from TA Instruments Thermogravimetric Analyzer, Discovery TGA5500 with autosampler. The general experimental conditions for TGA were: ramp from 25 °C to 300 °C at 10 °C/min; nitrogen purge gas flow at 25 mL/min; platinum sample holder. TGA analysis of (R)-3-cyclopentyl-3-hydrazineylpropanenitrile L-tartrate dehydrate (Compound 3a) crystalline sample revealed 10.3% weight loss below 100 °C due to dehydration decomposition above 120 °C. The TGA thermogram of Compound 3a crystalline sample is provided in Figure 13. Example 13: Preparation of Compound 1 phosphate Crude (3R)-Cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyraz ol-1- yl]propionitrile phosphate (crude Compound 1 phosphate):

A solution of crude (3R)-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4- yl)pyrazol-1-yl]propionitrile (Compound 1 free base, 18.7 g, 17.1 g theoretical, 55.8 mmol) generated from the previous process step in dichloromethane (DCM, 294 mL) and isopropanol (IPA, 12.8 mL) was heated to 36 °C before a solution of phosphoric acid (a 85% aqueous solution of H ₃ PO ₄ , 7.40 g, , 64.2 mmol, 1.15 equiv) in isopropanol (IPA, 12.7 mL) was added at 36 °C. A precipitate was formed almost immediately. The resulting mixture was then heated at 36 °C for 1 hour, then cooled gradually to ambient temperature and stirred at room temperature for 1 hour. The solids were collected by filtration, washed with DCM (2 x 50.8 mL) and n-heptane (22.6 mL), and dried in the vacuum oven at 40 - 45 °C to a constant weight to afford (3R)-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyraz ol-1-yl]propionitrile phosphate (crude Compound 1 phosphate, 23.04 g , 22.56 g theoretical, 102% yield) as white to off-white crystalline powders, which contained some residual phosphoric acid and were purified by recrystallization in a mixture of methanol (MeOH), isopropanol (IPA), and n-heptane in the subsequent step. For Compound 1 phosphate: ¹ H NMR (DMSO-d ₆ , 500 MHz) d ppm 12.10 (s, 1H), 8.78 (s, 1H), 8.68 (s, 1H), 8.36 (s 1H), 7.58 (dd, 1H, J = 1.9, 3.5 Hz), 6.97 (d, 1H, J = 3.6 Hz), 4.52 (td, 1H, J = 3.9, 9.7 Hz), 3.25 (dd, 1H, J = 9.8, 17.2 Hz), 3.16 (dd, 1H, J = 4.0, 17.0 Hz), 2.41, (m, 1H), 1.79 (m, 1H), 1.59 (m, 1H), 1.51 (m, 2H), 1.42 (m, 1H), 1.29 (m, 2H), 1.18 (m, 1H); ¹³ C NMR (DMSO-d ₆ , 125 MHz) d ppm 152.1, 150.8, 149.8, 139.2, 131.0, 126.8, 120.4, 118.1, 112.8, 99.8, 62.5, 44.3, 29.1, 29.0, 24.9, 24.3, 22.5; C ₁₇ H ₁₈ N ₆ (MW, 306.37 for free base) LCMS (EI) m/e 307 (M ⁺ + H, base peak), 329.1 (M ⁺ + Na). Purification of Crude Compound 1 Phosphate: (3R)-Cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyraz ol-1- yl]propionitrilephosphate (Compound 1 phosphate) A suspension of the crude Compound 1 phosphate (40.0 g, 100 mmol) in methanol (MeOH, 520 mL) is heated to 50 – 60 °C to generate a homogenous solution. The solution is polish filtered at 50 – 60 °C. Methanol (287 mL) is partially distilled at atmosphere pressure at 60 – 70 °C before IPA (320 mL) is added to the mixture at the same temperature to initiate crystallization of the final product (Compound 1 phosphate). n-Heptane (1000 mL) is then added to the mixture at 60 – 70 °C and the distillation is continued at atmospheric pressure at 60 – 70 °C. Once the distillation is complete, the mixture is stirred at 60 – 70 °C for 10 – 60 minutes before being gradually cooled to room temperature and stirred at room temperature for 3 – 6 hours. The solids are collected by filtration, washed sequentially with a mixture of IPA and n-heptane and n-heptane, and dried at 40 – 50 °C under vacuum to afford the final product, (Compound 1 phosphate, 39.4 g, 98.5%) as white crystalline powders. For Compound 1 phosphate: mp.197.6 °C; ¹ H NMR (DMSO-d ₆ , 500 MHz) δ ppm 12.10 (s, 1H), 8.78 (s, 1H), 8.68 (s, 1H), 8.36 (s 1H), 7.58 (dd, 1H, J = 1.9, 3.5 Hz), 6.97 (d, 1H, J = 3.6 Hz), 4.52 (td, 1H, J = 3.9, 9.7 Hz), 3.25 (dd, 1H, J = 9.8, 17.2 Hz), 3.16 (dd, 1H, J = 4.0, 17.0 Hz), 2.41, (m, 1H), 1.79 (m, 1H), 1.59 (m, 1H), 1.51 (m, 2H), 1.42 (m, 1H), 1.29 (m, 2H), 1.18 (m, 1H); ¹³ C NMR (DMSO-d ₆ , 125 MHz) δ ppm 152.1, 150.8, 149.8, 139.2, 131.0, 126.8, 120.4, 118.1, 112.8, 99.8, 62.5, 44.3, 29.1, 29.0, 24.9, 24.3, 22.5; C ₁₇ H ₁₈ N ₆ (MW, 306.37 for free base) LCMS (EI) m/e 307 (M ⁺ + H, base peak), 329.1 (M ⁺ + Na). Example 14: Preparation of 4-Chloro-7H-pyrrolo[2,3-d]pyrimidine (Compound 12a)

Step 1. 4,6-Dichloropyrimidine-5-carbaldehyde (Compound 9a): In a 5 L 4-neck flask equipped with a mechanical stirrer, an addition funnel, a condenser, a thermocouple, and a N2 sweep into an aqueous NaOH scrubbing solution, phosphorous oxychloride (POCl ₃ , 1 L, 10.572 mol, 4.82 equiv) was charged and cooled in an ice/salt bath. N,N-Dimethylformamide (DMF, 320 mL, 4.138 mol, 1.85 equiv) was then added dropwise to the flask at 0 ± 2 °C. After addition of approximately 100 mL of DMF over approximately 0.5 h, crystallization occurred and the reaction temperature was increased from 0 to 10 °C. Addition was stopped and the mixture was allowed to re-cool to approximately 2 °C. The remaining DMF was added over 2.5 h at below 8 °C. The suspension became very thick making stirring difficult. When addition of DMF was complete, the mixture was stirred at 3 – 5 °C for 0.5 h.4,6-Dihydroxypyrimidine (Compound 8a, 250 g, 2.232 mol) was added portion wise as a solid. After about one third of 4,6-dihydroxypyrimidine was added, the reaction mixture became more mobile and a slow exothermic phenomena occurred with the reaction temperature increasing to approximately 12 °C over 0.5 h. The remaining 4,6-dihydroxypyrimidine was added portion wise over 0.25 h with the reaction temperature increasing from 12 to 27 °C. The reaction temperature was maintained at 25 – 27 °C with intermittent cooling during which time the yellow suspension became thinner, then thicker once again. After the exothermic phenomenon subsided in about 1 h, the reaction mixture was heated slowly. At about 55 °C the reaction mixture became extremely thick and the second mild exothermic phenomenon was occurred. The heating mantle was removed while the reaction temperature continued to increase to about 63 °C and remained at this temperature for several minutes before dropping. Heating of the mixture was resumed until gentle reflux (about 100 °C) was attained. At about 95 °C a steady, fairly rapid evolution of HCl gas began and the reaction mixture gradually thinned and darkened. After about 0.5 h, a clear brown solution developed with the reflux temperature slowly increasing to 115 °C over 1.25 h. After a total of 2.5 h at reflux, the reaction mixture was cooled to ambient temperature and stirred overnight at ambient temperature. Excess amount of POCl3 (as much as possible) was removed under reduced pressure (bath temperature 45 – 50 °C). The thick residual brown oil was poured very slowly into cold H ₂ O (5 L) in a 20 L separation funnel, adding ice as needed to maintain the aqueous mixture near room temperature. The aqueous mixture was extracted with EtOAc (2 x 3 L followed by 1 x 2 L). The combined EtOAc extracts were washed with H ₂ O (2 x 2.5 L), saturated NaHCO ₃ aqueous solution (1 L), brine (1 L), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure (bath temperature at 35 °C) to afford the crude 4,6-dichloropyrimidine-5-carbaldehyde (Compound 9a, 270 g, 395 g theoretical, 68.4%) as yellow-orange solids. A 20 g portion of this crude material was purified by Kugelrohr distillation (oven temperature at 90 – 100 °C, 225 mTorr) to give 15.3 g of pure 4,6-dichloropyrimidine-5-carbaldehyde (Compound 9a) as white solids that turned yellow on standing at room temperature. For 4,6- Dichloropyrimidine-5-carbaldehyde: ¹ H NMR (300 MHz, CDCl ₃ ) δ 10.46 (s, 1H), 8.89 (s,1H) ppm. Step 2. 4-Amino-6-chloropyrimidine-5-carbaldehyde (Compound 10a): A solution of 7 M NH ₃ in MeOH (265 mL, 1.855 mol, 2.0 equiv) was added over 1.25 h to a solution of 4,6-dichloropyrimidine-5-carbaldehyde (Compound 9a, 163.7 g, 0.9301 mol) in toluene (3 L) at ambient temperature. The reaction temperature slowly increased from 20 to 26 °C and a yellow suspension formed. Mild cooling was applied to maintain the reaction temperature at below 26 °C. The suspension was stirred at ambient temperature for 3.5 h before the solids were collected by filtration. The solids were washed with EtOAc (1 L). The filtrate was concentrated under reduced pressure, and the solids were triturated with toluene and n-heptane (2:1 v/v, 600 mL), filtered and dried to give 71.1 g of 4-amino-6- chloropyrimidine-5-carbaldehyde as a yellow solid. The original solid filtered from the reaction mixture contained additional amount of 4-amino-6-chloropyrimidine-5- carbaldehyde. The product was extracted from the filtered solid by stirring in EtOAc (1.25 L) for 1.5 h, filtering, then stirring in THF (750 mL) for 1 h and filtering. Both EtOAc and THF filtrates were concentrated under reduced pressure, and the resulting solids were triturated with toluene and n-heptane (2:1 v/v, 450 mL), filtered and dried to give an additional 44.1 g of 4-amino-6-chloropyrimidine-5-carbaldehyde as yellow solids. The combined yield of 4-amino-6-chloropyrimidine-5-carbaldehyde (115.2 g, 146.5 g theoretical) was 78.6%. For 4-Amino-6-chloropyrimidine-5-carbaldehyde: ¹ HNMR (300 MHz, DMSO-d ₆ ) δ 10.23 (s, 1H), 8.71 (bs, 1H), 8.55 (bs, 1H), 8.39 (s, 1H) ppm; C5H4ClN3O (MW, 157.56), LCMS (EI) m/e 158 (M ⁺ + H). Step 3. 6-Chloro-5-(2-methoxyvinyl)pyrimidin-4-ylamine (Compound 11a): A suspension of (methoxymethyl)triphenylphosphonium chloride (276.0 g, 0.807 mol, 1.1 equiv) in THF (1.5 L) was cooled in an ice/salt bath to - 2 °C and 1 M potassium tert-butoxide (KO ^t Bu) in THF (807 mL, 0.807 mol, 1.1 equiv) was added over 1.5 hour at - 2 to - 3 °C. The deep red-orange mixture was stirred at - 2 to - 3 °C for 1 h.4-Amino-6-chloropyrimidine-5-carbaldehyde (Compound 10a, 115.2 g, 0.7338 mol, 1.0 equiv) was then added portion wise to the reaction mixture as a solid form using THF (200 mL) to rinse the container and funnel. During the addition the reaction temperature increased from - 3 to 13 °C and a brown color developed. When the reaction temperature dropped to 10 °C, the cooling bath was removed and the reaction mixture was allowed to warm to ambient temperature and stirred at ambient temperature for 42 h. The reaction mixture was cooled to - 2 °C before being quenched by the slow addition of saturated NH ₄ Cl aqueous solution (750 mL). The mixture was concentrated under reduced pressure to remove most of the THF. The residue was partitioned between EtOAc (3 L) and H ₂ O (1 L). The organic phase was filtered to remove insoluble material at the interface, then extracted with 2 N HCl (4 x 250 mL) followed by 3 N HCl (2 x 250 mL). The combined HCl extracts were back- extracted with EtOAc (500 mL) then filtered through Celite to remove insoluble material. The filtrate was cooled in an ice/brine bath, adjusted to pH 8 with a 6 N aqueous NaOH solution and extracted with EtOAc (3 x 1 L). The combined EtOAc extracts were washed with brine (1 L) dried over Na ₂ SO ₄ stirred with charcoal (10 g) and silica gel (10 g) for 1 h. The mixture was filtered through Celite, washing the Celite pad with EtOAc (1 L). The filtrate was concentrated, co-evaporating residual EtOAc with n-heptane (500 mL). The resulting tan solid was pumped under high vacuum for 2 h to afford crude 6-chloro-5-(2-methoxyvinyl)pyrimidin-4-ylamine (Compound 11a, 72.3 g, 136.2 g theoretical, 53.1%). The crude desired product Compound 11a was used in the following reaction without further purification. A sample of crude product Compound 11a (2.3 g) was purified by silica gel column chromatography on, eluting with 0 – 35% EtOAc/n-heptane to give 1.7 g of pure 6- chloro-5-(2-methoxyvinyl)pyrimidin-4-ylamine (Compound 11a) as white solids, which was found to be a 1 to 2 mixture of E/Z isomers. For 6-Chloro-5-(2- methoxyvinyl)pyrimidin-4-ylamine: ¹ H NMR (300 MHz, DMSO-d ₆ ) for E-isomer: δ 8.02 (s, 1H), 7.08 (bs, 2H), 6.92 (d, 1H, J = 13.1), 5.35 (d, 1H, J = 13.0 Hz), 3.68 (s, 3H) ppm and for Z-isomer: δ 8.06 (s, 1H), 7.08 (bs, 2H), 6.37 (d, 1H, J = 6.8 Hz), 5.02 (d, 1H, J = 6.7 Hz), 3.69 (s, 3H) ppm; C7H8ClN3O (MW, 185.61), LCMS (EI) m/e 186/188 (M ⁺ + H). Step 4. 4-Chloro-7H-pyrrolo[2,3-d]pyrimidine (Compound 12a): Concentrated aqueous hydrochloric acid (HCl, 5 mL) was added to a solution of crude 6-chloro-5-(2-methoxyvinyl)pyrimidin-4-ylamine (Compound 11a, 70.0 g, 0.3784 mol) in THF (700 mL) and the resulting reaction mixture was heated to reflux for 7.5 h. On warming a light suspension was formed that gradually re-dissolved. When the reaction was deemed complete as monitored by HPLC, the reaction mixture was cooled to ambient temperature and stirred at ambient temperature for overnight. Solid NaHCO ₃ (15 g) was added to the reaction mixture and the resulting mixture was stirred at ambient temperature for 1 h. Charcoal (7 g), silica gel (7 g) and Na ₂ SO ₄ (20 g) were added and the mixture was heated to 40 °C for 1 h. The mixture was then cooled to ambient temperature and filtered through Celite, washing the Celite pad with THF (1 L). The filtrate was concentrated under reduced pressure and the resulting solid was dried under reduced pressure to afford crude 4-chloro-7H- pyrrolo[2,3-d]pyrimidine (Compound 12a, 58.1 g, 58.1 g theoretical, 100%) as yellow-brown solids. This crude desired product Compound 12 was dissolved in EtOAc (1.0 L) at 50 – 55 °C and treated with activated charcoal (3 g). The mixture was filtered while warm through Celite and the Celite pad was washed with warm EtOAc (250 mL). The filtrate was concentrated to about 500 mL and the suspension was allowed to stand at ambient temperature for overnight. The suspension was subsequently cooled to 0 – 5 °C for 2 h before the solids were collected by filtration. The solids were dried to afford pure 4-chloro-7H-[pyrrolo[2,3-d]pyrimidine (Compound 12a, 54.5 g, 58.1 g theoretical, 94%) as yellow-brown crystals. For Compound 12a: ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.58 (bs, 1H), 8.58 (s, 1H), 7.69 (d, 1H, J = 3.5 Hz), 6.59 (d, 1H, J = 3.5 Hz) ppm; LCMS (EI) m/e 154/156 (M ⁺ + H). Example 15: Alternative Preparation of 4-Chloro-7H-pyrrolo[2,3-d]pyrimidine (Compound 12a) Step 1. Ethyl 2-cyano-4,4-diethoxybutanoate (Compound 14a): To a mixture of ethyl cyanoacetate (Compound 13a, 182 Kg, 1609 moles) and DMSO (325 Kg) was added portion-wise sodium tert-amyloxide ( ^t AmONa, 158.8 Kg) at 5 °C. The mixture was then warmed to 70 - 75 °C and ethyl cyanoacetate (191 Kg, 1689 moles; total 3298 moles, 5.0 equiv) was charged. The mixture was stirred at 70 - 75 °C for 30 minutes before bromoacetaldehyde diethyl acetal (130.4 Kg, 665.2 moles) was added. The resulting reaction mixture was then heated to 90 °C and agitated at 90 °C until the reaction was complete. The reaction mixture was cooled to 5 °C and a 16% aqueous solution of ammonium chloride (NH4Cl) was added. The mixture was agitated for 30 minutes before ethyl acetate (490 Kg) was charged. The organic phase was separated and washed with water (695 Kg). The aqueous phase was extracted with ethyl acetate (455 Kg). The combined organic phase was washed with a 17% aqueous solution of sodium chloride (NaCl, 318 Kg) and brine (325 Kg). The organic solution was dried over sodium sulfate (Na ₂ SO ₄ ) and filtered. The filtrate was concentrated under reduced pressure. The residue was dissolved in petroleum ether (390 Kg) and treated with charcoal at 60 °C. The mixture was filtered and the filtrate was concentrated to dryness to afford the crude ethyl 2-cyano-4,4-diethoxybutanoate (Compound 14a, 146.6 Kg, 152.5 Kg theoretical, 96.1%) as a yellow to brown oil, which was directly utilized in the subsequent reaction without further purification. Step 2. 7H-Pyrrolo[2,3-d]pyrimidin-4-ol (Compound 15a): To a reactor was charged a solution of 18% sodium ethoxide (EtONa) in ethanol (1558 Kg) and formamidine acetate (153.5 Kg, 1474.4 moles, ). The mixture was agitated at ambient temperature for 1 hour before ethyl 2-cyano-4,4- diethoxybutanoate (Compound 14a, 269.8 Kg, 1176.7 moles, 1.25 equiv) was charged. The reaction mixture was heated to 75 °C and agitated at 75 °C until no unreacted ethyl 2-cyano-4,4-diethoxybutanoate (Compound 14) was detected. The mixture was cooled to 0 °C and an aqueous solution of 21% ammonium chloride (NH ₄ Cl, 783 Kg) was charged. The resulting mixture was agitated at 0 °C for 30 minutes and concentrated under the reduced pressure. The residual solution was cooled to 20 – 30 °C and filtered. The cake was reslurried with water (493 Kg) and filtered. The solids were suspended in water (474 Kg) and the concentrated hydrochloric acid (HCl, 89.2 Kg) was added. The mixture was agitated at 20 °C for 1 hour and then warmed to 30 °C until the cyclization reaction was complete. The mixture was then cooled to 5 °C and an aqueous solution of ammonium hydroxide (NH ₄ OH, 72 Kg) was added. After addition, the mixture was agitated at 5 °C for 1 h and then filtered. The wet cake was washed with water and dried in a vacuum oven to afford 7H-Pyrrolo[2,3-d]pyrimidin-4-ol (Compound 15a, 99.6 Kg, 159 Kg theoretical, 62.6%) as off-white to yellow solids, which was used in the subsequent reaction without further purification. Step 3. 4-Chloro-7H-pyrrolo[2,3-d]pyrimidine (Compound 12a): 7H-Pyrrolo[2,3-d]pyrimidin-4-ol (Compound 15a, 99.6 Kg, 737 moles) was added to a solution of DIEA (128.4 Kg, 99.53 moles, 1.35 equiv) in toluene (500 Kg) at ambient temperature and the resulting mixture was cooled to 0 °C. POCl3 (338 Kg, 2202 moles, 3.0 equiv) was then added to the mixture at 0 °C and the resulting reaction mixture was heated to 70 °C and agitated at 70 °C until the reaction was complete. The reaction mixture was cooled to 30 °C and added water (3500 Kg), sodium carbonate (Na ₂ CO ₃ , 700 Kg) and 2-methyltetrahydrofuran (MeTHF, 1200 Kg). The resulting mixture was then filtered. The organic phase of the filtrate was separated and washed with brine (424 Kg), dried over sodium sulfate (Na ₂ SO ₄ ), and filtered. The filtrate was concentrated to remove approximately 1000 Kg of MeTHF. The remaining solution was treated with charcoal (28 Kg) at 60 °C for 1 hour and filtered. The filtrate was concentrated to a thick slurry, cooled to 0 °C, and filtered. The cake was dried under reduced pressure to afford pure 4-chloro-7H-pyrrolo[2,3- d]pyrimidine (Compound 12a, 71.9 Kg, 113.2 Kg theoretical, 63.5%) as yellow to brown crystals.4-Chloro-7H-pyrrolo[2,3-d]pyrimidine (Compound 12a) manufactured by this synthetic method is identical in every comparable aspect with the compound obtained by Example 14. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.58 (bs, 1H), 8.58 (s, 1H), 7.69 (d, 1H, J = 3.5 Hz), 6.59 (d, 1H, J = 3.5 Hz) ppm; LCMS (EI) m/e 154/156 (M ⁺ + H). Example 16. Preparation of 4-Methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 1a) A suspension of sodium hydride (NaH, 60% suspension in mineral oil, 309, 7726 mmol, 1.211 equiv) in THF (4.0 L) was cooled to 0 – 5 °C in an ice bath before 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (Compound 12a, 980.0 g, 6381 mmol) was charged. The mixture was agitated at 0 – 15 °C for 30 minutes before a solution of TBDMS-Cl (1165 g, 7728 mmol, 1.211 equiv) in THF was charged at 0 – 15 °C. The resulting mixture was agitated at 0 – 15 °C for 1 – 2 hours. The mixture was cooled to – 10 °C and Iron(III) acetylacetonate (Fe(acac) ₃ , 113 g, 319 mmol, 0.05 equiv) was charged. A solution of methylmagnesium bromide in THF (3260 mL, 9780 mmol, 1.53 equiv) was the slowly charged to the mixture and the internal temperature was controlled to below 15 °C. The resulting reaction mixture was agitated at 15 – 30 °C for 2 hours. Once the coupling reaction was complete, an aqueous solution of ammonium chloride (NH4Cl, 8.0 L) was charged to quench the reaction mixture and the internal temperature was controlled to below 10 °C during quenching. Methyl tert- butyl ether (MTBE, 5.0 L) was charged into the quenched reaction mixture and the resulting mixture was filtered through a Celite bed. The Celite bed was washed with MTBE (2 x 500 mL). The two phases of the combined filtrate and wash solution were separated and the aqueous phase was extracted with MTBE (2 x 5.0 L). The combined organic extracts were concentrated under the reduced pressure and the residue was dissolved in methanol (MeOH, 5.0 L). The solution was then treated with an aqueous solution of 26 – 28% ammonium hydroxide (NH4OH, 1.0 L) and the resulting mixture was agitated at 15 – 40 °C for 16 hours. When the N-TBDMS-deprotection reaction was complete, the reaction mixture was concentrated under reduced pressure and n- heptane (2 x 4.0 L) was charged to remove water under the azeotropic conditions. The residue was then treated with n-heptane (8.0 L) and the resulting mixture was agitated at ambient temperature for at least one hour. The solids were collected by filtration and washed with n-heptane (2 x 1.0 L) to afford the crude desired product, 4-methyl- 7H-pyrrolo[2,3-d]pyrimidine (Compound 1a, 840 g, 849.6 g theoretical, 98.9%), as brown powders, which was purified by recrystallization in a mixture of ethyl acetate and n-heptane. A solution of crude methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 1a, 1640 g) in methanol (MeOH, 8.0 L) was treated with charcoal (2.0 Kg) and the resulting mixture was agitated at ambient temperature for 16 hours. The mixture was filtered through a Celite bed and the Celite bed was washed with MeOH (2 x 8.0 L). The combined methanol solution was concentrated under the reduced pressure and the residue was added ethyl acetate (8.0 L). The resulting solution was concentrated under the reduced pressure to remove most of ethyl acetate (approximately 6.0 L) before n- heptane (8.0 L) was introduced. The resulting mixture was agitated at ambient temperature for 14 hours. The solids were collected by filtration, washed by a mixture of ethyl acetate and n-heptane followed by n-heptane, and dried to constant weight to afford the purified methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 1a, 1325 g, 1640 g theoretical, 80.8% for purification by recrystallization and 80% for overall) as yellow to light brown crystalline powders. For Compound 1a: ¹ H NMR (DMSO-d ₆ , 500 MHz) δ 12.10 (br s, 1H), 8.61 (s, 1H), 7.47 (dd, J = 3.3, 2.5 Hz, 1H), 6.62 (s, dd, J = 3.5, 1.7 Hz, 1H), 2.64 (s, 3H) ppm; ¹³ C NMR (DMSO-d ₆ , 125 MHz) δ 158.7, 151.3, 151.2, 126.5, 117.6, 99.6, 21.3 ppm; C ₇ H ₇ N ₃ (MW, 133.15) LCMS (EI) m/e 134.1 (M ⁺ + H, base peak). Example 17. Alternative Preparation of 4-Methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 1a) Step 1. 4-Methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 1a): A turbid mixture of potassium tert-butoxide (18.31 g, 163 mmol, 2.12 equiv) in THF (100 mL) was cooled in an ice bath before a solution of 4,4- dimethoxybutanenitrile (Compound 16a, 10.00 g, 77 mmol) and ethyl acetate (7.46 g, 85 mmol, 1.1 equiv) in THF (20 mL) were charged over 15 minutes. The mixture was allowed to warm to room temperature and stirred at ambient temperature for 3 hours.2-Acetyl-4,4-dimethoxybutanenitrile, generated in situ, was then treated with formamidine acetate (65.0 g, 624 mmol, 8.1 equiv), 1-butanol (80 mL) and triethyl orthoformate (56.2 mL, 337 mmol, 4.38 equiv) at ambient temperature. The resulting mixture was heated to 110 - 120 °C and stirred at 110 - 120 °C for 1 hour. Additional triethyl orthoformate (26.5 mL, 159 mmol, 2.06 equiv) was added. The mixture was stirred at 110 °C for additional 16 hours. Additional formamidine acetate (31.38 g, 302 mmol, 3.92 equiv) and triethyl orthoformate (56.5 mL, 115 mmol, 1.5 equiv) were added in three portions over 24 hours. The mixture was heated for an additional 24 hours and concentrated under the reduced pressure to a residue. The residue was treated with water (150 mL) and MeTHF (210 mL). The resulting mixture was passed through a bed of Celite (12 g). Two phases of the filtrate were separated and the aqueous phase was extracted with MeTHF (175 mL x 2). The combined organic extracts were concentrated under the reduced pressure, and the resulting residue was treated a solution of HCl in IPA (5.5 M, 50.8 g), water (31 mL), and concentrated HCl (12 M, 15.6 g). The mixture was stirred at room temperature for 3 days. A concentrated aqueous NH4OH solution (38.6 g, 28 - 30%) was added and the mixture was concentrated to a residue, which was triturated with THF (170 mL, 2 x 150 mL). Filtrates were combined and concentrated to a residue, which was dissolved in DCM (30 mL) and purified by column chromatography over silica gel (SiO ₂ , 120 g), eluting with 0 – 100% of EtOAc in DCM, to afford the desired product, 4-methyl-7H- pyrrolo[2,3-d]pyrimidine (Compound 1a, 5.1 g, 10.25 g theoretical, 49.8% for three steps), as an off-white crystalline solid, which is identical in every comparable aspect with the compound obtained by Example 16. Step 2. 2-Acetyl-4,4-dimethoxybutanamide (Compound 20a): A solution of 3-oxobutanamide (Compound 19a, 5.0 g, 49.5 mmol) in DMF (15 mL) was treated with cesium carbonate (Cs2CO ₃ , 16.11 g, 49.5 mmol, 1.0 equiv) at ambient temperature. The resulting mixture was stirred at ambient temperature.2- Bromo-1,1-dimethoxyethane (8.36 g, 49.5 mmol, 1.0 equiv) was then added to the mixture and the resulting reaction mixture was heated to 80 °C for 5 – 8 hours. The reaction mixture was cooled to ambient temperature and then quenched with water (20 mL). The quenched reaction mixture was then extracted with ethyl acetate (3 x 20 mL) and the combined organic extracts were washed with water (2 x 10 mL), dried with anhydrous sodium sulfate (Na ₂ SO ₄ ), and concentrated under reduced pressure. The residue was purified by silica gel (SiO ₂ ) column chromatography to afford 2- acetyl-4,4-dimethoxybutanamide (Compound 20a, 5.8 g, 9.37 g theoretical, 61.9%) as a thick oil, which contains some residual DMF. For 2-acetyl-4,4- dimethoxybutanamide: ¹ H NMR (DMSO-d ₆ , 400 MHz) δ 6.70 (s, 1H), 6.30 (s, 1H), 4.28 (dd, 1H), 3.47 (t, 1H), 3.23 (s, 6H), 2.25 (s, 3H), 2.19, (m, 1H), 2.00 (m 1H); C ₈ H ₁₅ NO ₄ (MW, 189.21), LCMS (EI) m/e 190.2 (M ⁺ + H). Step 3. 2-Acetyl-4,4-dimethoxybutanenitrile (Compound 17a): A solution of 2-acetyl-4,4-dimethoxybutanamide (Compound 20a, 1.0 g, 4.23 mmol) in DMF (4 mL) was treated with cyanuric chloride (Compound 21a, 0.39 g, 2.11 mmol, 0.5 equiv). The resulting reaction mixture was stirred at ambient temperature for 1 h. Once the reaction was complete, the reaction mixture was quenched with water (10 mL) and the quenched reaction mixture was extracted with ethyl acetate (3 x 10 mL). The combined organic extracts were washed with water (2 x 10 mL), dried with anhydrous sodium sulfate (Na ₂ SO ₄ ), and concentrated under reduced pressure. The residue was purified by silica gel (SiO ₂ ) column chromatography to afford 2-acetyl-4,4-dimethoxybutanenitrile (Compound 17a, 280 mg, 724 mg theoretical, 38.7%) as a thick oil. For 2-acetyl-4,4- dimethoxybutanenitrile: ¹ H NMR (DMSO-d ₆ , 400 MHz, a mixture of ketone and enol forms obtained) δ 10.7 (br. s, ½ H for enol form of –OH), 4.38 (m, 1H), 3.25 (m, 6H for two OMe and ½ H for ketone form of –CH-), 2.25 – 2.50 (m, 2H), 2.15 and 2.25 (s, 3H); C ₈ H ₁₃ NO ₃ (MW, 171.196), LCMS (EI) m/e 172.2 (M ⁺ + H).2-Acetyl-4,4- dimethoxybutanenitrile (Compound 17a) generated by this method reacts with formamidine acetate followed by treatment with HCl to afford 4-methyl-7H- pyrrolo[2,3-d]pyrimidine (Compound 1a) according to Example 16 described above. Example 18. Preparation of 4-Methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl) hydrochloride (Compound 1a hydrochloride) To a reactor under nitrogen were charged 2,4-dichloro-7H-pyrrolo[2,3- d]pyrimidine (Compound 22a, 200 g, 1.064 mole) and THF (1.2 L). The content in the reactor was cooled to below – 5 °C before 60% NaH in mineral oil (51 g, 1.28 moles, 1.2 equiv) was added portion wise. During addition of NaH, the internal temperature was maintained at – 5 to 5 °C. After the addition, agitation was continued for 30 minutes and then a solution of TBDMS-Cl (193 g, 1.28 moles, 1.2 equiv) in THF (200 mL) was added slowly by keeping the internal temperature at – 5 to 5 °C. Agitation of the reaction mixture was continued for 30 minutes and Fe(acac)3 (18.8 g, 53.2 mmol, 0.05 equiv) was then added followed by the addition of a 3.0 M solution of MeMgCl in THF (532 mL, 1.596 moles, 1.5 equiv) at – 5 to 5 °C. After the reaction mixture was kept for an additional 1 h, by which time IPC by HPLC showed the completion of the coupling reaction, the reaction mixture was poured into a solution of EDTA di-sodium salt dihydrate (200 g) in water (2.0 L) while the internal temperature was controlled at below 15 °C. The biphasic mixture was diluted with methyl tert-butyl ether (MTBE, 2.0 L), treated with Celite (150 g), and filtered by centrifuge. The solid cake was washed with MTBE and the filtrate was allowed for phase separation. The aqueous phase was separated and extracted with MTBE (1.0 L). The organic phase was combined and washed successively with 3% citric acid aqueous solution (2 × 400 mL) and brine (600 mL). After being dried over Na ₂ SO ₄ , the organic phase was filtered and concentrated to dryness. The residue was taken up with petroleum ether (2.0 L) and any insoluble materials were removed by filtration through a thin layer of silica gel. The filtrate was concentrated to give the crude desired product, 7-(tert-butyldimethylsilyl)-2-chloro-4-methyl-7H-pyrrolo[2,3 - d]pyrimidine (Compound 22a, 300 g), as an oily residue, which was used directly in the subsequent reaction without further purification. A mixture of crude 7-(tert-butyldimethylsilyl)-2-chloro-4-methyl-7H- pyrrolo[2,3-d]pyrimidine (Compound 22a, 300 g, 1.064 moles) and 5% palladium on carbon (Pd/C, 30 g) in methanol (1.8 L) was vigorously agitated under 1 atm of hydrogen at 50 - 55 °C for 3 hours. After IPC by HPLC confirmed the completion of the reaction, the reaction mixture was cooled to 20 – 25 °C and filtered. The filter cake was washed with methanol and the filtrate was concentrated to dryness. The residue was suspended in ethyl acetate (EtOAc, 225 mL) and agitated at 10 – 15 °C for 1 hour. The solids were collected by filtration, washed with ethyl acetate and dried under vacuum at 40 – 45 °C to give 4-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 1a hydrochloride, 151.5 g, 180.5 g theoretical, 84% yield for two steps) as light yellow crystalline powders. For Compound 1a hydrochloride: ¹ H NMR (DMSO-d ₆ , 500 MHz) δ ppm 13.54 (br s, 1H), 9.04 (s, 1H), 7.95 (dd, J = 3.4, 2.4 Hz, 1H), 7.13 (s, dd, J = 3.4, 1.5 Hz, 1H), 2.97 (s, 3H); ¹³ C NMR (DMSO-d ₆ , 125 MHz) δ ppm 154.0, 151.0, 144.0, 131.6, 117.2, 103.1, 17.6; C7H8ClN3 (MW, 169.61; C7H7N3 for free base, MW 133.15) LCMS (EI) m/e 134.1 (M ⁺ + H, base peak). Example 19. Preparation of Sodium 2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)acetate (5b) and 2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)acetic acid (Compound 5a) Step 1. 4-Chloro-7-tosyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 24a): A suspension of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (Compound 12a, 18.0 g, 117 mmol) in acetone (180 mL) was added a 50% aqueous sodium hydroxide solution (NaOH, 14.07 g, 176 mmol, 1.5 equiv) at ambient temperature. The resulting mixture was then agitated at ambient temperature until a clear solution was generated. p-Toluenesulfonyl chloride (pTsCl, 25.7 g, 135 mmol, 1.15 equiv) was added to the solution at ambient temperature and the resulting reaction mixture was agitated at ambient temperature for 1 hour. When the reaction was complete, the reaction mixture was filtered, and the solids were washed with acetone before being discarded. The filtrate was then concentrated under the reduced pressure, and the residue was treated with methyl tert-butyl ether (MTBE, 180 mL) and n-heptane (180 mL). The resulting mixture was agitated at ambient temperature for 1 hour. The solids were collected by filtration, washed with n-heptane (180 mL), and dried in the vacuum oven to the constant weight to afford the desired product, 4-chloro-7-tosyl-7H-pyrrolo[2,3- d]pyrimidine (Compound 24a, 32.1 g, 36.0 g theoretical, 89.2 % yield), as off-white powders, which was used in the subsequent reactions without further purification. For 4-Chloro-7-tosyl-7H-pyrrolo[2,3-d]pyrimidine: ¹ H NMR (DMSO-d ₆ , 400 MHz) δ 8.78 (s, 1H), 8.10 (d, 2H), 7.79 (d, 1H), 7.34 (d, 2H), 6.72 (d, 1H), 2.41 (s, 3H) ppm; C ₁₃ H ₁₀ ClN ₃ O ₂ S (MW, 307.75), LCMS (EI) m/e 308.1 (M ⁺ + H). Step 2. Diethyl 2-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)malonate (Compound 25a): A solution of 4-chloro-7-tosyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 24a, 7.0 g, 22.75 mmol) and diethyl malonate (5,46 g, 34.1 mmol, 1.5 equiv) in anhydrous DMF (30 mL) was treated with solid cesium carbonate (Cs ₂ CO ₃ , 18.53 g, 56.9 mmol, 2.5 equiv) at ambient temperature. The resulting reaction mixture was them warmed to 50 – 60 °C and agitated at 50 – 60 °C for 2 – 3 hours. When the reaction was complete, the reaction mixture was cooled to ambient temperature before being treated with water (H ₂ O, 80 mL). The quenched reaction mixture was then agitated at ambient temperature for 1 hour followed by at 0 – 5 °C for 1 hour. The solids were collected by filtration, washed with water (50 mL) followed by n-heptane (50 mL), and dried in the vacuum oven at 40 °C to constant weight to afford the desired product, diethyl 2-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)malonate (Compound 25a, 6.2 g, 9.81 g theoretical, 63.2 % yield), as off-white powders, which were used in the subsequent reactions without further purification. For Diethyl 2-(7-tosyl-7H- pyrrolo[2,3-d]pyrimidin-4-yl)malonate: ¹ H NMR (CDCl3, 400 MHz) δ 8.98 (s, 1H), 8.12 (d, 2H), 7.77 (d, 1H), 7.34 (d, 2H), 6.72 (d, 1H), 5.10 (s, 1H), 4.25 (m, 4H), 2.42 (s, 3H), 1.27 (m, 6H) ppm; C ₂₀ H ₂₁ N ₃ O ₆ S (MW, 431.46), LCMS (EI) m/e 432.3 (M ⁺ + H). Step 3. Ethyl 2-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)acetate (Compound 26a): A solution of diethyl 2-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)malonate (Compound 25a, 4.0 g, 9.27 mmol) in ethanol (EtOH, 20 mL) was treated with a solution of 21% sodium ethoxide in ethanol (NaOEt, 21 wt%, 0.30 g, 0.927 mmol, 0.10 equiv) at ambient temperature and the resulting reaction mixture was agitated at ambient temperature for 12 hours. The reaction mixture was quenched with a 0.1 N aqueous hydrochloric acid solution (10 mL) and the resulting mixture was concentrated under the reduced pressure. The residue was then purified by the silica gel (SiO ₂ ) column chromatography to afford the desired product, ethyl 2-(7-tosyl-7H- pyrrolo[2,3-d]pyrimidin-4-yl)acetate (Compound 26a, 2.08 g, 3.33 g theoretical, 62.6% yield), as off-white powders, which were used in the subsequent reaction without further purification. For Ethyl 2-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4- yl)acetate: ¹ H NMR (CDCl ₃ , 400 MHz) δ 8.96 (s, 1H), 8.11 (d, 2H), 7.75 (d, 1H), 7.33 (d, 2H), 6.70 (d, 1H), 4.19 (q, 2H), 4.30 (s, 2H), 2.41 (s, 3H), 1.25 (t, 3H) ppm; C17H17N3O ₄ S (MW, 359.40), LCMS (EI) m/e 360.2 (M ⁺ + H). Step 4. Ethyl 2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)acetate (Compound 27a): A solution of diethyl 2-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)malonate (Compound 25a, 4.0 g, 9.27 mmol) in ethanol (EtOH, 20 mL) was treated with a solution of 21% sodium ethoxide in ethanol (NaOEt, 21 wt%, 3.0 g, 9.27 mmol, 1.0 equiv) at ambient temperature. The resulting reaction mixture was heated to 65 – 75 °C and agitated at 65 – 75 °C for 12 hours. The reaction mixture was quenched with a 1.0 N aqueous hydrochloric acid solution and the resulting mixture was concentrated under the reduced pressure. The residue was then purified by the silica gel (SiO ₂ ) column chromatography to afford the desired product, ethyl 2-(7H-pyrrolo[2,3- d]pyrimidin-4-yl)acetate (Compound 27a, 1.3 g, 1.9 g theoretical, 68.3% yield), as off-white powders, which were used in the subsequent reactions without further purification. For Ethyl 2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)acetate: ¹ H NMR (CDCl3, 400 MHz) δ 11.40 (br s, 1H), 8.90 (s, 1H), 7.42 (d, 1H), 6.65 (d, 1H), 4.23 (q, 2H), 4.13 (s, 2H), 1.27 (t, 3H) ppm; C ₁₀ H ₁₁ N ₃ O ₂ (MW, 205.22), LCMS (EI) m/e 206.2 (M+ + H). Step 5. Sodium 2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)acetate (Compound 5b): A solution of ethyl 2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)acetate (Compound 27a,1.2 g, 5.85 mmol) in acetone (10 mL) and THF (10 mL) was treated with an aqueous solution of 6 N sodium hydroxide (6 N NaOH, 1.462 mL, 8.77 mmol, 1.5 equiv) at ambient temperature. The resulting reaction mixture was agitated at ambient temperature for 5 hours. The solids were collected by filtration and the isolated solids were suspended in methanol (MeOH, 4.0 mL). The resulting suspension was then added acetone (15 mL) and the mixture was agitated at ambient temperature for 1 hour. The solids were collected by filtration, washed with acetone (2 x 5 mL), and dried under vacuum to afford the desired product, sodium 2-(7H-pyrrolo[2,3- d]pyrimidin-4-yl)acetate (Compound 5b, 1.1 g, 1.164 g theoretical, 94.5% yield), as off-white powders, which was used in the subsequent reaction without further purification. For Sodium 2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)acetate: ¹ H NMR (DMSO-d ₆ , 400 MHz) δ 8.36 (s, 1H), 7.37 (d, 1H), 6.40 (d, 1H), 3.61 (s, 2H) ppm; C ₈ H ₆ N ₃ NaO ₂ (MW, 199.15; C ₈ H ₇ N ₃ O ₂ for the corresponding acid, MW 177.16), LCMS (EI) m/e 178.1 (M ⁺ + H). Step 6. 2-(7H-Pyrrolo[2,3-d]pyrimidin-4-yl)acetic acid (Compound 5a): A solution of ethyl 2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)acetate (Compound 27a, 1.2 g, 5.85 mmol) in acetone (10 mL) and THF (10 mL) was treated with an aqueous solution of 6 N sodium hydroxide (6 N NaOH, 1.462 mL, 8.77 mmol, 1.5 equiv) at ambient temperature. The resulting reaction mixture was agitated at ambient temperature for 5 hours. The reaction mixture was then treated with a solution of 1 N aqueous hydrochloric acid (1 N HCl, 9.0 mL) before being concentrated under the reduced pressure. The residue was then purified by the silica gel (SiO ₂ ) column chromatography to afford the desired product, 2-(7H-pyrrolo[2,3-d]pyrimidin-4- yl)acetic acid (Compound 5a, 0.83 g, 1.04 g theoretical, 79.8% yield), as off-white solids, which were used in the subsequent reaction without further purification. For 2- (7H-pyrrolo[2,3-d]pyrimidin-4-yl)acetic acid: ¹ H NMR (DMSO-d ₆ , 400 MHz) δ 12.01 (br s, 1H), 8.56 (s, 1H), 7.36 (d, 1H), 6.57 (d, 1H), 3.66 (s, 2H) ppm; C ₈ H ₇ N ₃ O ₂ (MW, 177.16), LCMS (EI) m/e 178.1 (M ⁺ + H). Various modifications of the invention, in addition to those described herein, will be apparent to those skilled in the art from the foregoing description. Such modifications are also intended to fall within the scope of the appended claims. Each reference, including all patent, patent applications, and publications, cited in the present application is incorporated herein by reference in its entirety.