PROCESO PARA LA PREPARACIÓN DE 6-(2-HIDROXI-2-METILPROPOXI)-4-(6-(6-((6-METHOXYPYRIDIN-3-IL)METIL)-3,6-DIAZABICICLO[3.1.1]HEPTAN-3-IL)PIRIDIN-3-IL)PIRAZOLO[1.5-A]PIRIDINA-3-CARBONITRILO

Abstract

Claim 1: A process for preparing a compound of formula (1) or a pharmaceutically acceptable salt thereof, said process characterized in that it comprises treating a compound of formula (2) or a salt thereof with 6-methoxynicotinaldehyde and a reducing agent to form the compound of formula (1) or a pharmaceutically acceptable salt thereof.

Description

Minutes P 18 01 02928 PROCESS FOR THE PREPARATION OF 6-(2-HYDROXY-2-METHYLPROPOXY)-4(6-(6-((6-METHOXYPIRIDIN-3-IL)METHYL)-3,6-DIAZABYCYCLO[3,1,1]HEPTAN-3IL)PYRIDIN-3-IL)PYRAZOLO[1,5-A]PYRIDINE-3-CARBONITRILE CROSS REFERENCE TO RELATED APPLICATIONS This application claims priority from Provisional Patent Application US No. 62 / 570,565, filed on October 10, 2017, the contents of which are incorporated herein by reference in their entirety. TECHNICAL FIELD This document provides processes and intermediates useful for the preparation of a compound of Formula I: or a pharmaceutically acceptable salt thereof. BACKGROUND The Formula I compound Yo 6-(2-hydroxy-2-methylpropoxy)-4-(6-(6-((6-methoxypyridin-3-yl)methyl)-3,6diazabicyclo[3,1,1]heptan-3-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile, including pharmaceutically acceptable salts thereof, exhibits inhibition of the rearranged receptor during transfection (RET) kinase. 233789 2665047 of 99 Minutes P 18 01 02928 There is a need to obtain alternative synthetic procedures for the preparation of the compound of Formula I and pharmaceutically acceptable salts thereof. Such alternative synthetic procedures are provided herein. SUMMARY OF THE INVENTION This document provides a process for preparing a compound of Formula I: or a pharmaceutically acceptable salt thereof. In some embodiments, the process comprises: treat a compound of formula 16 or a salt thereof with 6-methoxynicotinaldehyde and a reducing agent to form the compound of Formula I or a pharmaceutically acceptable salt thereof. In some embodiments, the process for preparing a compound of Formula I further comprises preparing the compound of formula 16, wherein the process comprises treating a compound of formula 15 or a salt thereof, wherein R1 is an amine protecting group, with a deprotecting agent to form the compound of formula 16 or a salt thereof. 233789 2665047 of 99 Minutes P 18 01 02928 In some embodiments, the process for preparing a compound of Formula I further comprises preparing the compound of formula 15 or a salt thereof, wherein R1 is an amine protecting group, wherein the process comprises: treat a compound of formula 13 or a salt thereof, wherein X represents a halogen or a sulfonate, with a compound of formula 14 or a salt thereof, wherein R1 is an amine protecting group, to form the compound of formula 15 or a salt thereof. In some embodiments, the process for preparing a compound of Formula I further comprises preparing the compound of formula 13 or a salt thereof, wherein the process comprises treating a compound of formula 20 or a salt thereof, wherein X represents a halogen or a sulfonate, with a compound of formula 21 233789 3 2665047 of 99 Acta P 18 01 02928 in the presence of 2,2-dimethyloxirane, a first catalyst comprising a metal, and a first weak base to form the compound of formula 13 or a salt thereof. In some embodiments, the process for preparing a compound of Formula I further comprises preparing the compound of formula 13 or a salt thereof, wherein the process comprises: a) treating a compound of formula 20 or a salt thereof with a first ester or diboronic acid in the presence of a second catalyst comprising a metal to form a compound of formula 22 or a salt thereof, wherein X represents a halogen or a sulfonate and R5 represents an ester or boronic acid with the boron atom as the point of attachment to the pyrazolopyridine ring of compound 22 or a salt thereof; b) treating the compound of formula 22 or a salt thereof with a first strong base and hydrogen peroxide to form a compound of formula 23 or a salt thereof, wherein X represents a halogen or a sulfonate; and c) treat the compound of formula 23 or a salt thereof with 2,2-dimethyloxirane in the presence of a second strong base to form the compound of formula 13 or a salt thereof. In some embodiments, the process for preparing a compound of Formula I further comprises preparing the compound of formula 13 or a salt thereof, wherein the process comprises: treat a compound of formula 35 233789 2665047 of 99 Minutes P 18 01 02928 or a salt thereof with a first triflation reagent to form a compound of formula 36 or a salt thereof; and treat the compound of formula 36 or a salt thereof with a compound of formula or a salt thereof, wherein X represents a halogen or a sulfonate and R6 represents an ester or boronic acid with the boron atom as the attachment point to the pyridine ring of compound 12, in the presence of a third catalyst comprising a metal to form the compound of formula 13 or a salt thereof. In some embodiments, the process for preparing a compound of Formula I further comprises preparing the compound of formula 35 or a salt thereof, wherein the process comprises: treat a compound of formula 33 or a salt thereof with 2,2-dimethyloxirane in the presence of a third strong base to form the compound of formula 34 233789 2665047 of 99 Minutes P 18 01 02928 or a salt thereof; and treat the compound of formula 34 or a salt thereof with a first dealkylating agent to form the compound of formula 35 or a salt thereof. In some embodiments, the process for preparing a compound of Formula I further comprises preparing the compound of formula 33 or a salt thereof, wherein the process comprises: treat a compound of formula A or a salt thereof with a second diboronic acid or ester in the presence of a fourth catalyst comprising a metal to form a compound of formula 32 or a salt thereof, wherein R9 represents an ester or boronic acid with the boron atom as the point of attachment to the pyrazolopyridine ring of compound 32 or a salt thereof; and treating the compound of formula 32 or a salt thereof with a first oxidizing agent to form the compound of formula 33 or a salt thereof. In some embodiments, the process for preparing a compound of Formula I further comprises preparing the compound of formula 20 or a salt thereof, wherein the process comprises: treat a compound of formula 19 233789 2665047 of 99 Act P 18 01 02928 or a salt thereof with a compound of formula 12 / =N R6 or a salt thereof, wherein X represents a halogen or a sulfonate and R6 represents an ester or boronic acid with the boron atom as the attachment point to the pyridine ring of compound 12, in the presence of an eighth catalyst comprising a metal to form the compound of formula 20 or a salt thereof. This document also provides a process for preparing a compound of Formula I or a pharmaceutically acceptable salt thereof, wherein the process comprises treating a compound of formula 29 or a salt thereof with a compound of formula 21 233789 2665047 of 99 Acta P 18 01 02928 in the presence of 2,2-dimethyl dioxirane, a sixth catalyst comprising a metal, and a second weak base to form the compound of Formula I or a pharmaceutically acceptable salt thereof. This document also provides a process for preparing a compound of Formula Yo I or a pharmaceutically acceptable salt thereof, wherein the process comprises: a) treating a compound of formula 29 or a salt thereof with a third ester or diboronic acid in the presence of a seventh catalyst comprising a metal to form a compound of formula 30 30 or a salt thereof, wherein R8 represents an ester or boronic acid with the boron atom as the point of attachment to the pyrazolopyridine ring of compound 30 or a salt thereof; b) treat the compound of formula 30 or a salt thereof with a fourth strong base and hydrogen peroxide to form a compound of formula 31 233789 2665047 of 99 Minutes P 18 01 02928 or a salt thereof; and c) treating the compound of formula 31 or a salt thereof with 2,2-dimethyloxirane in the presence of a fifth strong base to form the compound of Formula I or a pharmaceutically acceptable salt thereof. In some embodiments, the process for preparing a compound of Formula I further comprises preparing the compound of formula 29, wherein the process comprises: treating a compound of formula 19 or a salt thereof with a compound of formula 28 or a salt thereof, wherein R7 represents an ester or boronic acid with the boron atom as the attachment point to the pyridine ring of compound 28, in the presence of a fifth catalyst comprising a metal to form the compound of formula 29 or a salt thereof. In some embodiments, the process for preparing a compound of Formula I further comprises preparing the compound of formula 19 or a salt thereof, wherein the process comprises: treat a compound of formula A 233789 2665047 of 99 Minutes P 18 01 02928 or a salt thereof with a second dealkylating agent to form a compound of formula 18 or a salt thereof; and treat the compound of formula 18 or a salt thereof with a second triflation reagent to form the compound of formula 19 or a salt thereof. In some embodiments, the process for preparing a compound of Formula I further comprises preparing the compound of formula A or a salt thereof by a process comprising: a) treat a compound of formula 1a Br 1a or a salt thereof with O-(mesethylsulfonyl)hydroxylamine to form a compound of formula 2a (b) treating the compound of formula 2a with acrylonitrile or an acrylonitrile derivative in the presence of a first non-nucleophilic base to form the compound of formula A; or, alternatively, preparing the compound of formula A or a salt thereof by a process comprising: a) treat a compound of formula 8A 233789 2665047 of 99 Minutes P 18 01 02928 8A or a salt thereof with O-(2,4-dinitrophenyl)hydroxylamine to form a compound of formula 9A b) treating the compound of formula 9A with acrylonitrile or an acrylonitrile derivative in the presence of a first non-nucleophilic base to form the compound of formula A. In some embodiments, the process for preparing a compound of Formula I further comprises preparing the compound of formula 15 or a salt thereof, wherein R1 is an amine protecting group, comprising: treating a compound of formula 26 or a salt thereof, wherein R1 is an amine protecting group, with 2,2-dimethyloxirane in the presence of a sixth strong base to form the compound of formula 15 or a salt thereof. In some embodiments, the process for preparing a compound of Formula I further comprises preparing the compound of formula 26 or a salt thereof, wherein the process comprises: 233789 2665047 of 99 Minutes P 18 01 02928 a) treat a compound of formula B or a salt thereof with a compound of formula 24 R3 N-R1 or a salt thereof, wherein R1 is an amine protecting group and R3 represents an ester or boronic acid with the boron atom as the attachment point to the pyridine ring of compound 24, in the presence of a ninth catalyst comprising a metal to form a compound of formula 25 or a salt thereof; and b) treating the compound of formula 25 with a fourth ester or diboronic acid in the presence of a tenth catalyst comprising a metal to form a mixture, and treating the mixture with a seventh strong base and hydrogen peroxide to form the compound of formula 26 or a salt thereof. In some embodiments, the process for preparing a compound of Formula I further comprises preparing the compound of formula B or a salt thereof by a process comprising: a) treat a compound of formula 8 N. or a salt thereof with O-(mesethylsulfonyl)hydroxylamine to form the compound of formula 9 233789 2665047 of 99 Minutes P 18 01 02928 9; and b) treating the compound of formula 9 with acrylonitrile or an acrylonitrile derivative in the presence of a second non-nucleophilic base to form a mixture, and treating the mixture with a second oxidant to form the compound of formula B. In some embodiments of the process for preparing a compound of Formula I provided herein, the reducing agent is selected from the group consisting of an alkali metal borohydride, a hydrazine compound, citric acid, a citric acid salt, succinic acid, a succinic acid salt, ascorbic acid, and an ascorbic acid salt. In some embodiments, the reducing agent is selected from the group consisting of sodium borohydride, lithium borohydride, nickel borohydride, and potassium borohydride. In some embodiments, the reducing agent is sodium triacetoxyborohydride (STAB). In some embodiments of the process for preparing a compound of Formula I provided herein, the deprotecting agent is selected from the group consisting of trifluoroacetic acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, phosphoric acid, sulfuric acid, methanesulfonic acid, p-toluenesulfonic acid, acetyl chloride, aluminum trichloride, and boron trifluoride. In some embodiments, the deprotecting agent is sulfuric acid. In some embodiments of the process for preparing a compound of Formula I provided herein, X is a halogen selected from the group consisting of F, Br, Cl, and I. In some embodiments, X is F. In some embodiments, X is a sulfonate selected from the group consisting of triflate, mesylate, and tosylate. In some embodiments of the process for preparing a compound of Formula I provided herein, R1 is an amine protecting group selected from the group consisting of formyl, acetyl, trifluoroacetyl, benzyl, benzoyl, carbamate, benzyloxycarbonyl, p-methoxybenzyl carbonyl, tert-butyloxycarbonyl (Boc), trimethylsilyl, 2-trimethylsilylethanesulfonyl, trityl and substituted trityl groups, allyloxycarbonyl, 9-fluorenylmethyloxycarbonyl, nitroveratryloxycarbonyl, p-methoxybenzyl, and tosyl. In some embodiments, R1 is tert-butyloxycarbonyl (Boc). 233789 2665047 of 99 Minutes P 18 01 02928 In some embodiments of the process for preparing a compound of Formula I provided herein, the metal of the first catalyst is selected from the group consisting of nickel, palladium, and platinum. In some embodiments, the first catalyst is a palladium catalyst selected from the group consisting of Pd(dba)2, PdCl2, Pd(OAc)2, Pd(dppf)Cl2, Pd2(dba)3, PdChfCHsCNh, PdCh(PPh3)2, Pd(t-Bu)3, Pd(dppf)ChOH2Cl2, Pd(PPh3)4, Pd(OAc) / PPh3, PdCh[(Pet3)]2, Pd(DIPHOS)2, PdCl2(Bipy), [PdCl(Ph2PCH2PPh2)]2, PdCl2[P(o-Tol)3]2, Pd2(dba)3 / P(o-Tol)3, Pd2(dba) / P(furyl)3, PdCl2[P(furyl)3]2, PdCl2(PMePh2)2, PdCl2[P(4-F-Ph)3]2, PdCl2[P(C6F6)3]2, PdCl2[P(2-COOH-Ph)(Ph)2]2, and PdCl2[P(4-COOH-Ph)(Ph)2]2. In some embodiments, the first catalyst is Pd2(dba)3. In some embodiments of the process for preparing a compound of Formula I provided herein, the first weak base is selected from the group consisting of a carbonate, a bicarbonate, methylamine, ammonia, trimethylammonia, pyridine, and aniline. In some embodiments, the first weak base is cesium carbonate (Cs₂CO₃). In some embodiments of the process for preparing a compound of Formula I provided herein, the metal of the second catalyst is selected from the group consisting of nickel, palladium, and platinum. In some embodiments, the second catalyst is a palladium catalyst selected from the group consisting of Pd(dba)2, PdCl2, Pd(OAc)2, Pd(dppf)Cl2, Pd2(dba)3, PdCl2(CH3CN)2, PdCl2(PPh3)2, Pd(t-Bu)3, Pd(dppf)ChOH2Cl2, Pd(PPh3)4, Pd(OAc) / PPh3, PdCh[(Pet3)]2, Pd(DIPHOS)2, PdCl2(Bipy), [PdCl(Ph2PCH2PPh2)]2, PdCl2[P(o-Tol)3]2, Pd2(dba)3 / P(o-Tol)3, Pd2(dba) / P(furyl)3, PdCl2[P(furyl)3]2, PdCl2(PMePh2)2, PdCl2[P(4-F-Ph)3]2, PdCl2[P(C6F6)3]2, PdCl2[P(2-COOH-Ph)(Ph)2]2, and PdCl2[P(4-COOH-Ph)(Ph)2]2. In some embodiments, the second catalyst is Pd(dppf)Cl2^CH2Cl2. In some embodiments of the process for preparing a compound of Formula I provided herein, the first ester or diboronic acid is selected from the group consisting of an alkenyl boronic acid, an alkyl boronic acid, an aryl boronic acid, a heteroaryl boronic acid, and a pinacol boronic ester. In some embodiments, the first ester or diboronic acid is bis(pinacolate)diboron. In some embodiments of the process for preparing a compound of Formula I provided herein, the first strong base and the second strong base are independently selected from the group consisting of lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, calcium hydroxide, 233789 14 2665047 of 99 Acta P 18 01 02928 strontium hydroxide, and barium hydroxide. In some embodiments, the first strong base is sodium hydroxide. In some embodiments, the second strong base is sodium hydroxide. In some embodiments of the process for preparing a compound of Formula I provided herein, R5 is pinacol ester of boronic acid represented by the formula: where the wavy line indicates the point of attachment to the pyrazolo[1,5-a]pyridine ring of compound 22. In some embodiments of the process for preparing a compound of Formula I provided herein, the first triflating agent is selected from the group consisting of N-phenyl-bis(trifluoromethanesulfonimide), N-(5-chloro-2-pyridyl)triflamide, N-(2-pyridyl)triflamide, trifluoromethanesulfonic anhydride, a trialkylsilyl triflate, and a trialkylstanyl triflate. In some embodiments, the first triflating agent is N-phenyl-bis(trifluoromethanesulfonimide). In some embodiments of the process for preparing a compound of Formula I provided herein, the metal of the third catalyst is selected from the group consisting of nickel, palladium, and platinum. In some embodiments, the third catalyst is a palladium catalyst selected from the group consisting of Pd(dba)2, PdCl2, Pd(OAc)2, Pd(dppf)Cl2, Pd2(dba)3, PdChfCHsCNh, PdCh(PPh3)2, Pd(t-Bu)3, Pd(dppf)ChOH2Cl2, Pd(PPh3)4, Pd(OAc) / PPh3, PdCh[(Pet3)]2, Pd(DIPHOS)2, PdCl2(Bipy), [PdCl(Ph2PCH2PPh2)]2, PdCl2[P(o-Tol)3]2, Pd2(dba)3 / P(o-Tol)3, Pd2(dba) / P(furyl)3, PdCl2[P(furyl)3]2, PdCl2(PMePh2)2, PdCl2[P(4-F-Ph)3]2, PdCl2[P(C6F6)3]2, PdCl2[P(2-COOH-Ph)(Ph)2]2, and PdCl2[P(4-COOH-Ph)(Ph)2]2. In some embodiments, the third catalyst is Pd(dppf)Cl2^CH2Cl2. In some embodiments of the process for preparing a compound of Formula I provided herein, the third strong base is selected from the group consisting of lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, calcium hydroxide, strontium hydroxide, and barium hydroxide. In some embodiments, the third strong base is sodium hydroxide. In some embodiments of the process for preparing a compound of Formula I provided herein, the first dealkylating agent is selected from the group that 233789 15 2665047 of 99 Acta P 18 01 02928 consists of Lewis acids and nucleophilic reagents. In some embodiments, the first dealkylating agent is selected from the group consisting of boron trihalides, organoboranes, triiodides, trialkylsilyl halides, hexafluorosilicate, aluminum trihalides, lithium halides, hydrogen halides, iron trihalides, tin tetrahalides, titanium tetrahalides, thiolates, and amides. In some embodiments, the first dealkylating agent is a thiolate generated from dodecanethiol and sodium hydroxide. In some embodiments of the process for preparing a compound of Formula I provided herein, the second ester or diboronic acid is selected from the group consisting of an alkenyl boronic acid, an alkyl boronic acid, an aryl boronic acid, a heteroaryl boronic acid, and a pinacol boronic ester. In some embodiments, the second ester or diboronic acid is bis(pinacolate)diboron. In some embodiments of the process for preparing a compound of Formula I provided herein, the metal of the fourth catalyst is selected from the group consisting of nickel, palladium, and platinum. In some embodiments, the fourth catalyst is a palladium catalyst selected from the group consisting of Pd(dba)2, PdCl2, Pd(OAc)2, Pd(dppf)Cl2, Pd2(dba)3, PdChCCHjCNk, PdCh(PPh3)2, Pd(t-Bu)3, Pd(dppf)ChOH2Cl2, Pd(PPh3)4, Pd(OAc) / PPh3, PdCh[(Pet3)]2, Pd(DIPHOS)2, PdCl2(Bipy), [PdCl(Ph2PCH2PPh2)]2, PdCl2[P(o-Tol)3]2, Pd2(dba)3 / P(o-Tol)3, Pd2(dba) / P(furyl)3, PdCl2[P(furyl)3]2, PdCl2(PMePh2)2, PdCl2[P(4-F-Ph)3]2, PdCl2[P(C6F6)3]2, PdCl2[P(2-COOH-Ph)(Ph)2]2, and PdCl2[P(4-COOH-Ph)(Ph)2]2. In some embodiments, the fourth catalyst is Pd(dppf)Cl2^CH2Cl2. In some embodiments of the process for preparing a compound of Formula I provided herein, R9 is pinacol ester of boronic acid represented by the formula: where the wavy line indicates the point of attachment to the pyridine ring of compound 32. In some embodiments of the process for preparing a compound of Formula I provided herein, the first oxidizing agent is selected from the group consisting of O2, N-methylmorpholine N-oxide (NMO), chloranyl (CA), 7,7,8,8-tetracyanoquinodimethane (TCNQ), benzylidene-malononitrile (BMCN), tetracyanoethylene (TCNE), 2,3-dicyano-1,4-benzoquinone (DCBQ), and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). In some embodiments, the first oxidizing agent is NMO. 233789 16 2665047 of 99 Minutes P 18 01 02928 In some embodiments of the process for preparing a compound of Formula I provided herein, R6 is pinacol ester of boronic acid represented by the formula: where the wavy line indicates the point of attachment to the pyridine ring of compound 12. In some embodiments of the process for preparing a compound of Formula I provided herein, the metal of the eighth catalyst is selected from the group consisting of nickel, palladium, and platinum. In some embodiments, the eighth catalyst is a palladium catalyst selected from the group consisting of Pd(dba)2, PdCl2, Pd(OAc)2, Pd(dppf)Cl2, Pd2(dba)3, PdChfCHsCNh, PdCh(PPh3)2, Pd(t-Bu)3, Pd(dppf)ChOH2Cl2, Pd(PPh3)4, Pd(OAc) / PPh3, PdCh[(Pet3)]2, Pd(DIPHOS)2, PdCl2(Bipy), [PdCl(Ph2PCH2PPh2)]2, PdCl2[P(o-Tol)3]2, Pd2(dba)3 / P(o-Tol)3, Pd2(dba) / P(furyl)3, PdCl2[P(furyl)3]2, PdCl2(PMePh2)2, PdCl2[P(4-F-Ph)3]2, PdCl2[P(C6F6)3]2, PdCl2[P(2-COOH-Ph)(Ph)2]2, and PdCl2[P(4-COOH-Ph)(Ph)2]2. In some embodiments, the eighth catalyst is Pd(dppf)Cl2^CH2Cl2. In some embodiments of the process for preparing a compound of Formula I provided herein, the metal of the sixth catalyst is selected from the group consisting of nickel, palladium, and platinum. In some embodiments, the sixth catalyst is a palladium catalyst selected from the group consisting of Pd(dba)2, PdCl2, Pd(OAc)2, Pd(dppf)Cl2, Pd2(dba)3, PdCl2(CH3CN)2, PdCl2(PPh3)2, Pd(t-Bu)3, Pd(dppf)ChOH2Cl2, Pd(PPh3)4, Pd(OAc) / PPh3, PdCh[(Pet3)]2, Pd(DIPHOS)2, PdCl2(Bipy), [PdCl(Ph2PCH2PPh2)]2, PdCl2[P(o-Tol)3]2, Pd2(dba)3 / P(o-Tol)3, Pd2(dba) / P(furyl)3, PdCl2[P(furyl)3]2, PdCl2(PMePh2)2, PdCl2[P(4-F-Ph)3]2, PdCl2[P(C6F6)3]2, PdCl2[P(2-COOH-Ph)(Ph)2]2, and PdCl2[P(4-COOH-Ph)(Ph)2]2. In some embodiments, the sixth catalyst is Pd2(dba)3. In some embodiments of the process for preparing a compound of Formula I provided herein, the second weak base is selected from the group consisting of a carbonate, a bicarbonate, methylamine, ammonia, trimethylammonia, pyridine, and aniline. In some embodiments, the second weak base is cesium carbonate. In some forms of carrying out the process to prepare a compound of Formula As provided herein, the third boronic acid is selected from the group consisting of an alkenyl boronic acid, an alkyl boronic acid, an aryl boronic acid, an acid 233789 17 2665047 of 99 Acta P 18 01 02928 heteroaryl boronic acid, and a pinacol boronic ester. In some embodiments, the third boronic acid or ester is bis(pinacolato)diboron. In some embodiments of the process for preparing a compound of Formula I provided herein, the metal of the seventh catalyst is selected from the group consisting of nickel, palladium, and platinum. In some embodiments, the seventh catalyst is a palladium catalyst selected from the group consisting of Pd(dba)2, PdCl2, Pd(OAc)2, Pd(dppf)Cl2, Pd2(dba)3, PdChfCHsCNk, PdCh(PPh3)2, Pd(t-Bu)3, Pd(dppf)ChOH2Cl2, Pd(PPh3)4, Pd(OAc) / PPh3, PdCh[(Pet3)]2, Pd(DIPHOS)2, PdCl2(Bipy), [PdCl(Ph2PCH2PPh2)]2, PdCl2[P(o-Tol)3]2, Pd2(dba)3 / P(o-Tol)3, Pd2(dba) / P(furyl)3, PdCl2[P(furyl)3]2, PdCl2(PMePh2)2, PdCl2[P(4-F-Ph)3]2, PdCl2[P(C6F6)3]2, PdCl2[P(2-COOH-Ph)(Ph)2]2, and PdCl2[P(4-COOH-Ph)(Ph)2]2. In some embodiments, the seventh catalyst is Pd(dppf)Cl2^CH2Cl2. In some embodiments of the process for preparing a compound of Formula I provided herein, R8 is pinacol ester of boronic acid represented by the formula: where the wavy line indicates the point of attachment to the pyridine ring of compound 30. In some embodiments of the process for preparing a compound of Formula I provided herein, the fourth and fifth strong bases are each independently selected from the group consisting of lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, calcium hydroxide, strontium hydroxide, and barium hydroxide. In some embodiments, the fourth strong base is sodium hydroxide. In some embodiments, the fifth strong base is sodium hydroxide. In some embodiments of the process for preparing a compound of Formula I provided herein, R7 is pinacol ester of boronic acid represented by the formula: where the wavy line indicates the point of attachment to the pyridine ring of compound 28. In some embodiments of the process for preparing a compound of Formula I provided herein, the fifth catalyst metal is selected from the group consisting of nickel, palladium, and platinum. In some embodiments, the fifth catalyst 233789 18 2665047 of 99 Acta P 18 01 02928 is a palladium catalyst selected from the group consisting of Pd(dba)2, PdCl2, Pd(OAc)2, Pd(dppf)Cl2, Pd2(dba)3, PdChCCHjCNk, PdCb(PPh3)2, Pd(t-Bu)3, Pd(dppf)CUCH2Cl2, Pd(PPh3)4, Pd(OAc) / PPh3, PdCh[(Pet3)]2, Pd(DIPHOS)2, PdCl2(Bipy), [PdCl(Ph2PCH2PPh2)]2, PdCb[P(o-Tol)3]2, Pd2(dba> / P(o-Tol)3, Pd2(dba) / P(furyl)3, PdCl2[P(furyl)3]2, PdCh(PMePh2)2, PdCl2[P(4-F-Ph)3]2, PdCl2[P(C6F6)3]2, PdCl2[P(2-COOH-Ph)(Ph)2]2, and PdCl2[P(4-COOH-Ph)(Ph)2]2. In some embodiments, the fifth catalyst is Pd(dppf)CUCH2Cl2. In some embodiments of the process for preparing a compound of Formula I provided herein, the second triflation reagent is selected from the group consisting of N-phenyl-bis(trifluoromethanesulfonimide), N-(5-chloro-2-pyridyl)triflamide, N-(2-pyridyl)triflamide, trifluoromethanesulfonic anhydride, a trialkylsilyl triflate, and a trialkylstanyl triflate. In some embodiments, the second triflation reagent is N-phenyl-bis(trifluoromethanesulfonimide). In some embodiments of the process for preparing a compound of Formula I provided herein, the second dealkylating agent is selected from the group consisting of Lewis acids and nucleophilic reagents. In some embodiments, the second dealkylating agent is selected from the group consisting of boron trihalides, organoboranes, triiodides, trialkylsilyl halides, hexafluorosilicate, aluminum trihalides, lithium halides, hydrogen halides, iron trihalides, tin tetrahalides, titanium tetrahalides, thiolates, and amides. In some embodiments, the second dealkylating agent is a thiolate generated from dodecanethiol and sodium hydroxide. In some embodiments of the process for preparing a compound of Formula I provided herein, the first non-nucleophilic base is selected from the group consisting of triethylamine (TEA), diisopropylethylamine (DIPEA), N-methylmorpholine (NMM), tri-tert-butylpyrimidine (TTBP), 1,4-diazabicyclo-[2,2,2]octane (DABCO), 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU), N,N-diethylaniline, pyridine, 2,6-lutidine, 2,4,6-cholidine, 4-dimethylaminopyridine, quinuclidine, 2,6-di-tert-butylpyridine, tert-butylphosphacene, lithium diisopropylamide, sodium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, lithium tetramethylpiperidide, sodium hydride, potassium hydride, sodium tert-butoxide, and potassium tert-butoxide. In some embodiments, the first non-nucleophilic base is DBU. In some embodiments of the process for preparing a compound of Formula I provided herein, acrylonitrile or an acrylonitrile derivative is 2-chloroacrylonitrile. 233789 19 2665047 of 99 Minutes P 18 01 02928 In some embodiments of the process for preparing a compound of Formula I provided herein, the sixth strong base is selected from the group consisting of lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, calcium hydroxide, strontium hydroxide, and barium hydroxide. In some embodiments, the sixth strong base is potassium hydroxide. In some embodiments of the process for preparing a compound of Formula I provided herein, R3 is pinacol ester of boronic acid represented by the formula: where the wavy line indicates the point of attachment to the pyridine ring of compound 24. In some embodiments of the process for preparing a compound of Formula I provided herein, the ninth catalyst metal and the tenth catalyst metal are independently selected from the group consisting of nickel, palladium, and platinum. In some embodiments, the ninth catalyst is a palladium catalyst selected from the group consisting of Pd(dba)2, PdCl2, Pd(OAc)2, Pd(dppf)Cl2, Pd2(dba)3, PdCl2(CH3CN)2, PdCh(PPh3)2, Pd(t-Bu)3, Pd(dppf)Ch-CH2Ch, Pd(PPh3)4, Pd(OAc) / PPh3, PdCl2[(Pet3)]2, Pd(DIPHOS)2, PdCh(Bipy), [PdCl(Ph2PCH2PPh2)]2, PdCl2[P(o-Tol)3]2, Pd2(dba)3 / P(o-Tol)3, Pd2(dba) / P(furyl)3, PdCl2[P(furyl)3]2, PdCl2(PMePh2)2, PdCl2[P(4-F-Ph)3]2, PdCh[P(C6F6)3]2, PdCl2[P(2-COOH-Ph)(Ph)2]2, and PdCl2[P(4-COOH-Ph)(Ph)2]2. In some embodiments, the ninth catalyst is Pd(dppf)Cl2^CH2Cl2. In some embodiments, the tenth catalyst is a palladium catalyst selected from the group consisting of Pd(dba)2, PdCl2, Pd(OAc)2, Pd(dppf)Cl2, Pd2(dba)3, PdCl2(CH3CN)2, PdCl2(PPh3)2, Pd(t-Bu)3, Pd(dppf)ChOH2Cl2, Pd(PPh3)4, Pd(OAc) / PPh3, PdCh[(Pet3)]2, Pd(DIPHOS)2, PdCl2(Bipy), [PdCl(Ph2PCH2PPh2)]2, PdCl2[P(o-Tol)3]2, Pd2(dba)3 / P(o-Tol)3, Pd2(dba) / P(furyl)3, PdCl2[P(furyl)3]2, PdCl2(PMePh2)2, PdCl2[P(4-F-Ph)3]2, PdCl2[P(C6F6)3]2, PdCl2[P(2-COOH-Ph)(Ph)2]2, and PdCl2[P(4-COOH-Ph)(Ph)2]2. In some embodiments, the tenth catalyst is Pd(dbbf). In some embodiments of the process for preparing a compound of Formula I provided herein, the fourth diboronic acid is selected from the group consisting of an alkenylboronic acid, an alkylboronic acid, an arylboronic acid, an acid 233789 2665047 of 99 Acta P 18 01 02928 heteroaryl boronic acid, and a pinacol boronic ester. In some embodiments, the fourth ester or diboronic acid is bis(pinacolato)diboron. In some embodiments of the process for preparing a compound of Formula I provided herein, the seventh strong base is selected from the group consisting of lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, calcium hydroxide, strontium hydroxide, and barium hydroxide. In some embodiments, the seventh strong base is sodium hydroxide. In some embodiments of the process for preparing a compound of Formula I provided herein, the second non-nucleophilic base is selected from the group consisting of triethylamine (TEA), diisopropylethylamine (DIPEA), N-methylmorpholine (NMM), tri-tert-butylpyrimidine (TTBP), 1,4-diazabicyclo-[2,2,2]octane (DABCO), 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU), N,N-diethylaniline, pyridine, 2,6-lutidine, 2,4,6-cholidine, 4-dimethylaminopyridine, quinuclidine, 2,6-di-tert-butylpyridine, tert-butylphosphacene, lithium diisopropylamide, sodium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, lithium tetramethylpiperidide, sodium hydride, potassium hydride, sodium tert-butoxide, and potassium tert-butoxide. In some embodiments, the second non-nucleophilic base is DIPEA. In some embodiments of the process for preparing a compound of Formula I provided herein, the second oxidizing agent is selected from the group consisting of O2, N-methylmorpholine N-oxide (NMO), chloranyl (CA), 7,7,8,8-tetracyanoquinodimethane (TCNQ), benzylidene-malononitrile (BMCN), tetracyanoethylene (TCNE), 2,3-dicyano-1,4-benzoquinone (DCBQ), and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). In some embodiments, the second oxidizing agent is DDQ. In some embodiments of the process for preparing a Formula I compound provided herein, the process further comprises mixing the Formula I compound or a pharmaceutically acceptable salt thereof with a pharmaceutically acceptable carrier to form a pharmaceutical composition. A compound of formula 20a is also provided herein. 20a 233789 2665047 of 99 Act P 18 01 02928 or pharmaceutically acceptable salt thereof. A compound of formula 25a is also provided herein. 25a or a pharmaceutically acceptable salt thereof. A compound of formula 26a is also provided herein. 26a or a pharmaceutically acceptable salt thereof. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by a person skilled in the art to which this invention pertains. The methods and materials described herein are for use in the present invention; other suitable methods and materials known in the art may also be used. The materials, methods, and examples are illustrative only and are not intended to be limiting. All publications, patent applications, patents, sequences, database entries, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, this specification, including the definitions, shall prevail. Other features and advantages of the invention will become apparent from the following detailed description and figures, and from the claims. DETAILED DESCRIPTION Definitions As used herein, a strong base refers to a basic chemical compound that is capable of deprotonating weak acids in an acid-base reaction. Examples of 233789 2665047 of 99 Strong bases include, but are not limited to, hydroxides, alkoxides, and ammonia. Common examples of strong bases are the hydroxides of alkali and alkaline earth metals; for example, NaOH. Certain strong bases are even capable of deprotonating very weakly acidic C—H groups in the absence of water. Strong bases include, but are not limited to, sodium hydroxide, potassium hydroxide, barium hydroxide, cesium hydroxide, calcium hydroxide, strontium hydroxide, lithium hydroxide, and rubidium hydroxide. In some embodiments, NaOH is used as the strong base. As used herein, the term weak base refers to organic and inorganic bases that are only partially ionized in aqueous solution. Weak bases typically have a pKa between approximately 6 and approximately 11. A large number of such weak bases are known and are exemplified by those listed in the Handbook of Biochemistry and Molecular Biology, vol. 1, 3rd ed., G.D. Fassman, CRC Press, 1976, pp. 305–347. A weak base may be soluble or insoluble in water.Suitable weak bases include, but are not limited to, alkali metal carbonates and bicarbonates, such as sodium carbonate, potassium carbonate, cesium carbonate, and sodium bicarbonate; ammonia; primary amines, such as methylamine; secondary amines; and tertiary amines, such as trialalkylamines, for example, trimethylamine, triethylamine, tripropylamine, and tributylamine, benzyldiethylamine, pyridine, quinoline, N-methylmorpholine, aniline, and the like. A non-nucleophilic base, as used herein, refers to a base that will not act as a nucleophile; that is, a base that will not donate an electron pair to an electrophile to form a chemical bond in a reaction. Typically, non-nucleophilic bases are bulky and sterically hindered, so that protons can bind to the basic center, but alkylation and complexation are prevented. Examples of non-nucleophilic bases include, but are not limited to, amines and nitrogen heterocycles such as triethylamine and pyridine, amidines, lithium compounds, and phosphazenes. Other examples of non-nucleophilic bases include sodium hydride and potassium hydride. As used herein, the term “amine protecting group” means any group known in organic synthesis for the protection of amine groups. Such amine protecting groups include those listed in Greene, “Protective Groups in Organic Synthesis,” John Wiley & Sons, New York (1981), and “The Peptides: Analysis, Synthesis, 233789 2665047 of 99 Minutes P 18 01 02928 Biology, Vol. 3,” Academic Press, New York (1981). Any amine protecting group known in the art may be used. Examples of amine protecting groups include, but are not limited to, the following: (1) acyl types such as formyl, trifluoroacetyl, phthalyl, and p-toluenesulfonyl; (2) aromatic carbamate types such as benzyloxycarbonyl (Cbz) and substituted benzyloxycarbonyls, 1-(p-biphenyl)-1-methylethoxycarbonyl, and 9-fluorenylmethyloxycarbonyl (Fmoc); (3) aliphatic carbamate types such as tert-butyloxycarbonyl (Boc), ethoxycarbonyl, diisopropylmethoxycarbonyl, and allyloxycarbonyl; (4) cyclic alkyl carbamate types such as cyclopentyloxycarbonyl and adamantyloxycarbonyl; (5) types of alkyl such as triphenylmethyl and benzyl; (6) trialkylsilane such as trimethylsilane; (7) thiol-containing types such as phenylthiocarbonyl and dithiasuccinoyl; and (8) alkyl types such as triphenylmethyl, methyl, and benzyl;and substituted alkyl types such as 2,2,2-trichloroethyl, 2-phenylethyl, and t-butyl; and trialkylsilane types such as trimethylsilane. The term “deprotecting agent” as used herein refers to a reagent or system of reagents (reagent(s) and solvent) useful for removing a protecting group. Deprotecting agents may be acids, bases, or reducing agents. For example, the removal of the benzyl group (Bn) can be carried out by reduction (hydrogenolysis), while the removal of carbamates (e.g., the Boc group) can be carried out using acids (e.g., HCl, TFA, H₂SO₄, etc.), optionally with gentle heating. As used herein, the phrase reducing agent refers generically to any species capable of reducing another species while itself being oxidized. As used herein, the phrase oxidizing agent or oxidant refers generically to any species capable of oxidizing another species while itself being reduced. As used herein, the term triflation reagent refers to a compound useful in a reaction in which a triflate group is attached to a hydroxyl group to form a triflate ester. The triflation agent is the source of the trifluoroacetyl group. Triflation reagents include, but are not limited to, trialkylsilyl triflates, trialkylstanyl triflates, triflic anhydride (trifluoromethanesulfonic anhydride), N-phenyl-bis(trifluoromethanesulfonimide) (PhNTf2), N-(5-chloro-2-pyridyl)triflimide, and (2-pyridyl)triflimide. An acrylonitrile derivative as used herein is a compound derived from acrylonitrile, having the formula CH2CHCN, where one of the hydrogen atoms has 233789 2665047 of 99 Acta P 18 01 02928 has been replaced by another group or atom. An example of an acrylonitrile derivative is 2chloroacrylonitrile, where one of the hydrogen atoms of acrylonitrile has been replaced by a chlorine atom. As used herein, the term dilute, when used with respect to an acid solution, refers to a solution that has an acid concentration of less than approximately 0.1 N. The terms “hydrogen” and “H” are used interchangeably herein. The terms “halogen” or “halo” refer to fluorine (F), chlorine (Cl), bromine (Br), or iodine (I). As used herein, the term alkyl refers to a hydrocarbon chain, which may be linear or branched, containing the indicated number of carbon atoms. For example, C1-6 indicates that the group may have from 1 to 6 carbon atoms (inclusive). Examples include methyl, ethyl, isopropyl, tert-butyl, and n-hexyl. As used herein, the term “alkylamine” refers to an amine containing one or more alkyl groups. An alkylamine can be a primary amine, a secondary amine, or a tertiary amine. For example, a secondary amine is an amine containing two alkyl groups. Diisopropylethylamine is an example. As used herein, the singular forms “un”, “una”, “el” and “la” include their plural references, unless the context indicates otherwise. As used herein, ranges and quantities may be expressed as “approximately” a particular value or range. “Approximately” also includes the exact amount. Thus, “approximately 5 grams” means both “approximately 5 grams” and “5 grams.” It is also understood that ranges expressed herein include whole numbers within the ranges and fractions thereof. For example, a range of 5 grams to 20 grams includes whole number values ​​such as 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, and 20 grams, and fractions within the range including, but not limited to, 5.25, 6.5, 8.75, and 11.95 grams. As used herein, “optionally” means that the event or circumstance described below either occurs or does not occur, and that the description includes instances where the event or circumstance occurs and instances where it does not. For example, a reaction mixture that “optionally includes a catalyst” means that the reaction mixture either contains a catalyst or does not contain a catalyst. 233789 2665047 of 99 Minutes P 18 01 02928 A salt can be formed from a compound in any manner familiar to a person skilled in the art. Accordingly, the reference "forming a compound or a salt thereof" includes embodiments where a compound is formed and the salt is subsequently formed from the compound in a manner familiar to a person skilled in the art. It is noted that certain features of the invention, which are described, for clarity, in the context of separate embodiments, can also be provided in combination in a single embodiment. Conversely, several features of the invention, which are described, for brevity, in the context of a single embodiment, can also be provided separately or in any suitable sub-combination. All combinations of embodiments pertaining to the aspects described herein are specifically encompassed by the present invention as if each and every combination were explicitly stated individually, to the extent that such combinations encompass possible aspects. Furthermore, all subcombinations of embodiments contained within the aspects described herein, as well as all subcombinations of embodiments contained within all other aspects described herein, are also specifically included in the present invention as if each and every subcombination of all embodiments were explicitly stated herein. Process for preparing the Formula I compound In some embodiments, a process is provided herein for preparing a compound of Formula I or a pharmaceutically acceptable salt thereof. In some embodiments, the process for preparing a compound of Formula I or a pharmaceutically acceptable salt thereof comprises treating a compound of formula 16 233789 2665047 of 99 Minutes P 18 01 02928 or a salt thereof with 6-methoxynicotinaldehyde and a reducing agent to form the compound of Formula I or a pharmaceutically acceptable salt thereof. In some embodiments, the reducing agent is selected from an alkali metal borohydride, a hydrazine compound, citric acid, a citric acid salt, succinic acid, a succinic acid salt, ascorbic acid, and an ascorbic acid salt. In some embodiments, the reducing agent is selected from sodium borohydride, lithium borohydride, nickel borohydride, and potassium borohydride. In some embodiments, the lithium borohydride is selected from lithium borohydride and lithium triethylborohydride. In some embodiments, the sodium borohydride is selected from sodium triacetoxyborohydride (STAB), sodium borohydride, and sodium cyanoborohydride. In some embodiments, the reducing agent is STAB. In some embodiments, the process further comprises preparing a compound of formula 16. In some embodiments, the process for preparing a compound of formula 16 includes treating a compound of formula 15 or a salt thereof, wherein R1 is an amine protecting group, with a deprotecting agent to form the compound of formula 16 or a salt thereof. In some embodiments, R1 is an amine protecting group selected from formyl, acetyl, trifluoroacetyl, benzyl, benzoyl, carbamate, benzyloxycarbonyl, p-methoxybenzyl carbonyl, tert-butyloxycarbonyl (Boc), trimethylsilyl, 2-trimethylsilylethanesulfonyl, trityl and substituted trityl groups, allyloxycarbonyl, 9 233789 2665047 of 99 Acta P 18 01 02928 fluorenylmethyloxycarbonyl, nitroveratryloxycarbonyl, p-methoxybenzyl and tosyl. In some embodiments, R1 is tert-butyloxycarbonyl (Boc). In some embodiments, the deprotecting agent is selected from trifluoroacetic acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, phosphoric acid, sulfuric acid, methanesulfonic acid, p-toluenesulfonic acid, acetyl chloride, aluminum trichloride, and boron trifluoride. In some embodiments, the deprotecting agent is sulfuric acid. In some embodiments, the deprotecting agent is hydrochloric acid. In some embodiments, a process is provided herein for preparing a compound of formula 15 or a salt thereof, wherein R1 is an amine protecting group. In some embodiments, the process for preparing a compound of formula 15 comprises treating a compound of formula 13 or a salt thereof, wherein X represents a halogen or a sulfonate, with a compound of formula 14 R1i NH or a salt thereof, wherein R1 is an amine protecting group, to form the compound of formula 15 or a salt thereof. In some embodiments, X is a halogen. 233789 2665047 of 99 Acta P 18 01 02928 example, X is selected from the group consisting of F, Cl, Br, and I. In some embodiments, X is F. In some embodiments, X is a sulfonate. For example, X is selected from the group consisting of triflate, mesylate, and tosylate. In some embodiments of preparing a compound of formula 15, R1 is an amine protecting group selected from formyl, acetyl, trifluoroacetyl, benzyl, benzoyl, carbamate, benzyloxycarbonyl, p-methoxybenzyl carbonyl, tert-butyloxycarbonyl (Boc), trimethylsilyl, 2-trimethylsilylethanesulfonyl, trityl and substituted trityl groups, allyloxycarbonyl, 9-fluorenylmethyloxycarbonyl, nitroveratryloxycarbonyl, p-methoxybenzyl, and tosyl. In some embodiments, R1 is tert-butyloxycarbonyl (Boc). In some embodiments, the process further comprises preparing the compound of formula 13 or a salt thereof. In some embodiments, the process for preparing the compound of formula 13 or a salt thereof comprises treating a compound of formula 20 N=\ Or a salt thereof, wherein X represents a halogen or a sulfonate, with a compound of formula 21 Me ITEM Me'x^xYx^X' P(tBu)2iPrxJ\ / iPr tj iPr in the presence of 2,2-dimethyldioxirane, a first catalyst comprising a metal, and a first weak base to form the compound of formula 13 or a salt thereof. In some embodiments, X is a halogen. For example, X is selected from the group consisting of F, Cl, Br, and I. In some embodiments, X is F. In some embodiments, X is a sulfonate. For example, X is selected from the group consisting of triflate, mesylate, and tosylate. 233789 29 2665047 of 99 Minutes P 18 01 02928 In some embodiments, the first metal-comprising catalyst may be a nickel catalyst, a palladium catalyst, or a platinum catalyst. In some embodiments, the catalyst is a nickel catalyst. Examples of nickel catalysts include, but are not limited to, Raney nickel, supported nickel catalysts, Ponder nickel catalysts, nickel alloys, dichlorobis(tributylphosphine)nickel(II), bis(tricyclohexylphosphine)nickel(II) dichloride, tetrakis(triphenylphosphite)nickel(0), Ni(COD)2, Ni(PPh3)4, Ni(PPh3)2Cl2, Ni(acac)2, Cl2Ni(PMe3)2, Cl2Ni(PEt3)2, ChNi(Me2PPh)2, Cl2Ni(MePPh2)2, and Cl2Ni(Me2PCH2CH2PMe2). In some embodiments, the catalyst is a platinum catalyst. Examples of platinum catalysts include, but are not limited to, platinum carbonyl cyclovinylmethylsiloxane complexes, platinum divinyltetramethyldisiloxane complexes, platinum cyclovinylmethylsiloxane complexes, platinum octanaldehyde / octanol complexes, platinum olefin complexes, chloroplatinic acid olefin complexes, Karstedt's catalyst (Pt2[[(CH2=CH)(CH3)2Si]2O]3), Ashby's catalyst (Pt4[CH2=CHSi(CH3)O]4), a Lamoreaux catalyst (a Ptoctanal / octanol complex), platinum chloride, chloroplatinic acid, finely divided platinum metal (“platinum black”), platinum oxide, platinum metal on graphitized carbon, bis(acetylacetonato)platinum, (n5-cyclopentadienyl)trialkylplatinum, finely divided platinum oxide, PtO2 (“Adam's catalyst”), and chloroplatinic acid hexahydrate (Speier catalyst).In some embodiments, the catalyst is a palladium catalyst. In some embodiments, the first catalyst is a palladium catalyst selected from Pd(dba)2, PdCl2, Pd(OAc)2, Pd(dppf)Cl2, Pd2(dba)3, PdCl2(CH3CN)2, PdCl2(PPh3)2, Pd(t-Bu)3, Pd(dppf)Ch-CH2Cl2, Pd(PPh3)4, Pd(OAc) / PPh3, PdCh[(Pet3)]2, Pd(DIPHOS)2, PdCl2(Bipy), [PdCl(Ph2PCH2PPh2)]2, PdCl2[P(o-Tol)3]2, Pd2(dba)3 / P(oTol)3, Pd2(dba) / P(furyl)3, PdCl2[P(furyl)3]2, PdCl2(PMePh2)2, PdCl2[P(4-F-Ph)3]2, PdCl2[P(C6F6)3]2, PdCl2[P(2-COOH-Ph)(Ph)2]2, and PdCl2[P(4-COOH-Ph)(Ph)2]2. In some embodiments, the first catalyst comprising a metal is Pd2(dba)3. In some embodiments, the first weak base is selected from a carbonate, a bicarbonate, methylamine, ammonia, trimethylammonia, pyridine, and aniline. Examples of carbonates include, but are not limited to, calcium carbonate, lithium carbonate, sodium carbonate, potassium carbonate, and cesium carbonate. Examples of bicarbonates include, but are not limited to, sodium bicarbonate, potassium bicarbonate, cesium bicarbonate, magnesium bicarbonate, calcium bicarbonate, and hydrogen bicarbonate. 233789 30 2665047 of 99 Acta P 18 01 02928 ammonium. In some embodiments, the first weak base is cesium carbonate (CS2CO3). In some embodiments, the process for preparing the compound of formula 13 or a salt thereof comprises treating a compound of formula 20 or a salt thereof with a first ester or diboronic acid in the presence of a second catalyst comprising a metal to form a compound of formula 22 or a salt thereof, wherein X represents a halogen or a sulfonate and R5 represents an ester or boronic acid with the boron atom as the attachment point to the pyrazolopyridine ring of compound 22 or a salt thereof. In some embodiments, X is a halogen. For example, X is selected from the group consisting of F, Cl, Br, and I. In some embodiments, X is F. In some embodiments, X is a sulfonate. For example, X is selected from the group consisting of triflate, mesylate, and tosylate. In some embodiments, the first ester or diboronic acid is selected from an alkenylboronic acid, an alkylboronic acid, an arylboronic acid, a heteroarylboronic acid, and a pinacol boronic ester. In some embodiments, the first ester or diboronic acid is bis(pinacolato)diboron. In some embodiments, the second metal catalyst may be a nickel catalyst, a palladium catalyst, or a platinum catalyst. In some embodiments, the catalyst is a nickel catalyst. Examples of nickel catalysts include, but are not limited to, Raney nickel, supported nickel catalysts, Ponder nickel catalysts, nickel alloys, dichlorobis(tributylphosphine)nickel(II), bis(tricyclohexylphosphine)nickel(II) dichloride, tetrakis(triphenylphosphite)nickel(0), Ni(COD)2, Ni(PPh3)4, Ni(PPh3)2Cl2, Ni(acac)2, Cl2Ni(PMe3)2, Cl2Ni(PEt3)2, Cl2Ni(Me2PPh)2, Cl2Ni(MePPh2)2, and Cl2Ni(Me2PCH2CH2PMe2). In some embodiments, the catalyst is a platinum catalyst. Examples of platinum catalysts include, but are not limited to, platinum carbonyl cyclovinylmethylsiloxane complexes, platinum divinyltetramethyldisiloxane complexes, platinum cyclovinylmethylsiloxane complexes, and complexes of 233789 2665047 of 99 Acta P 18 01 02928 platinum octanaldehyde / octanol, platinum olefin complexes, chloroplatinic acid olefin complexes, Karstedt catalyst (Pt2[[(CH2=CH)(CH3)2Si]2O]3), catalyst of Ashby (Pt4[CH2=CHSi(CH3)O]4), a Lamoreaux catalyst (a Ptoctanal / octanol complex), platinic chloride, chloroplatinic acid, finely divided platinum metal (“platinum black”), platinum oxide, platinum metal on graphitized carbon, bis(acetylacetonato)platinum, (n5-cyclopentadienyl)trialkylplatinum, finely divided platinum oxide, PtO2 (“Adam catalyst”), and chloroplatinic acid hexahydrate (Speier catalyst). In some embodiments, the catalyst is a palladium catalyst.In some embodiments, the second catalyst is a palladium catalyst selected from Pd(dba)2, PdCl2, Pd(OAc)2, Pd(dppf)Cl2, Pd2(dba)3, PdCl2(CH3CN)2, PdCl2(PPh3)2, Pd(t-Bu)3, Pd(dppf)Ch-CH2Ch, Pd(PPh3)4, Pd(OAc) / PPh3, PdCh[(Pet3)]2, Pd(DIPHOS)2, PdCl2(Bipy), [PdCl(Ph2PCH2PPh2)]2, PdCl2[P(o-Tol)3]2, Pd2(dba)3 / P(oTol)3, Pd2(dba) / P(furyl)3, PdCl2[P(furyl)3]2, PdCl2(PMePh2)2, PdCl2[P(4-F-Ph)3]2, PdCl2[P(C6F6)3]2, PdCl2[P(2-COOH-Ph)(Ph)2]2, and PdCl2[P(4-COOH-Ph)(Ph)2]2. In some embodiments, the second catalyst comprising a metal is Pd(dppf)ChOH2Cl2. In some embodiments, R5 is a boronic acid or ester. In some embodiments, the boronic acid or ester is selected from an alkenyl boronic acid, an alkyl boronic acid, an aryl boronic acid, a heteroaryl boronic acid, and a pinacol boronic ester. In some embodiments, the boronic acid or ester is the pinacol ester of boronic acid. In some embodiments, the boronic acid or ester is represented by the formula R5, where the wavy line indicates the point of attachment to the pyrazolo[1,5-a]pyridine ring of compound 22 or a salt thereof. In some embodiments, R5 is pinacol boronic acid ester and compound 22 is compound 22a or get out of it. 233789 2665047 of 99 Minutes P 18 01 02928 In some embodiments, the process for preparing a compound of formula 13 further comprises treating the compound of formula 22 or a salt thereof with a first strong base and hydrogen peroxide to form a compound of formula 23 N^\ Ñ^A^CN HO or a salt thereof, wherein X represents a halogen or a sulfonate. In some embodiments, X is a halogen. For example, X is selected from the group consisting of F, Cl, Br, and I. In some embodiments, X is F. In some embodiments, X is a sulfonate. For example, X is selected from the group consisting of triflate, mesylate, and tosylate. In some embodiments, the first strong base is an alkali metal or alkaline earth metal hydroxide. For example, the first strong base is selected from lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, calcium hydroxide, strontium hydroxide, and barium hydroxide. In some embodiments, the first strong base is sodium hydroxide. In some embodiments, the process for preparing a compound of formula 13 further comprises treating the compound of formula 23 or a salt thereof with 2,2-dimethyloxirane in the presence of a second strong base to form the compound of formula 13 or a salt thereof. In some embodiments, the second strong base is an alkali metal or alkaline earth metal hydroxide. For example, the first strong base is selected from lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, calcium hydroxide, strontium hydroxide, and barium hydroxide. In some embodiments, the second strong base is sodium hydroxide. In some embodiments, the process for preparing the compound of formula 13 or a salt thereof comprises treating a compound of formula 35 233789 2665047 of 99 Acta P 18 01 02928 or a salt thereof with a first triflation reagent to form a compound of formula 36 or a salt of it. In some embodiments, the first triflating agent is selected from N-phenyl-bis(trifluoromethanesulfonimide), N-(5-chloro-2-pyridyl)triflamide, N-(2-pyridyl)triflamide, trifluoromethanesulfonic anhydride, a trialkylsilyl triflate, and a trialkylstanyl triflate. In some embodiments, the first triflating agent is N-phenyl-bis(trifluoromethanesulfonimide). In some embodiments, the process for preparing the compound of formula 13 or a salt thereof further comprises treating the compound of formula 36 or a salt thereof with a compound of formula 12 or a salt thereof, wherein X represents a halogen or a sulfonate and R6 represents an ester or boronic acid with the boron atom as the attachment point to the pyridine ring of compound 12, in the presence of a third catalyst comprising a metal to form the compound of formula 13 or a salt thereof. In some embodiments, X is a halogen or a sulfonate. For example, X is selected from the group consisting of F, Cl, Br, and I. In some embodiments, X is F. In some embodiments, X is a sulfonate. For example, X is selected from the group consisting of triflate, mesylate, and tosylate. In some embodiments, R6 is an ester or boronic acid. In some embodiments, the ester or boronic acid is pinacol, the ester of boronic acid. In some embodiments, the ester or boronic acid is represented by the formula , , where the wavy line indicates the point of attachment to the pyridine ring of compound 12 or a salt thereof. 233789 2665047 of 99 Minutes P 18 01 02928 In some embodiments, R6 is pinacol boronic acid ester and compound 12 is compound 12a 12a or salt of it. In some embodiments, the third metal catalyst may be a nickel catalyst, a palladium catalyst, or a platinum catalyst. In some embodiments, the catalyst is a nickel catalyst. Examples of nickel catalysts include, but are not limited to, Raney nickel, supported nickel catalysts, Ponder nickel catalysts, nickel alloys, dichlorobis(tributylphosphine)nickel(II), bis(tricyclohexylphosphine)nickel(II) dichloride, tetrakis(triphenylphosphite)nickel(0), Ni(COD)2, Ni(PPh3)4, Ni(PPh3)2Cl2, Ni(acac)2, Cl2Ni(PMe3)2, Cl2Ni(PEt3)2, ChNi(Me2PPh)2, CbNi(MePPh2)2, and Cl2Ni(Me2PCH2CH2PMe2). In some embodiments, the catalyst is a platinum catalyst. Examples of platinum catalysts include, but are not limited to, platinum carbonyl cyclovinylmethylsiloxane complexes, platinum divinyltetramethyldisiloxane complexes, platinum cyclovinylmethylsiloxane complexes, platinum octanaldehyde / octanol complexes, platinum olefin complexes, chloroplatinic acid olefin complexes, Karstedt's catalyst (Pt2[[(CH2=CH)(CH3)2Si]2O]3), Ashby's catalyst (Pt4[CH2=CHSi(CH3)O]4), a Lamoreaux catalyst (a Ptoctanal / octanol complex), platinum chloride, chloroplatinic acid, finely divided platinum metal (“platinum black”), platinum oxide, platinum metal on graphitized carbon, bis(acetylacetonato)platinum, (n5-cyclopentadienyl)trialkylplatinum, finely divided platinum oxide, PtO2 (“Adam's catalyst”), and chloroplatinic acid hexahydrate (Speier catalyst).In some embodiments, the catalyst is a palladium catalyst. In some embodiments, the palladium catalyst is selected from Pd(dba)2, PdCl2, Pd(OAc)2, Pd(dppf)Cl2, Pd2(dba)3, PdCl2(CH3CN)2, PdCl2(PPh3)2, Pd(t-Bu)3. Pd(dppf)ChOH2Cl2, Pd(PPh3)4, Pd(OAc) / PPh3, PdCh[(Pet3)]2, Pd(DIPHOS)2, PdCl2(Bipy), [PdCl(Ph2PCH2PPh2)]2, PdCl2[P(o-Tol)3]2, Pd2(dba)3 / P(o-Tol)3, Pd2(dba) / P(furyl)3, PdCl2[P(furyl)3]2, PdCl2(PMePh2)2, PdCl2[P(4-F-Ph)3]2, 233789 2665047 of 99 Minutes P 18 01 02928 PdCl2[P(C6F6)3]2, PdCl2[P(2-COOH-Ph)(Ph)2]2, and PdCl2[P(4-COOH-Ph)(Ph)2]2. In some embodiments, the third catalyst comprising a metal is Pd(dppf)CUCH2Cl2. In some embodiments, the process for preparing the compound of formula 13 comprises preparing the compound of formula 35 or a salt thereof. In some embodiments, the process comprises treating a compound of formula 33 or a salt thereof with 2,2-dimethyloxirane in the presence of a third strong base to form the compound of formula 34 or a salt of it. In some embodiments, the third strong base is selected from lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, calcium hydroxide, strontium hydroxide, and barium hydroxide. In some embodiments, the third strong base is sodium hydroxide. In some embodiments, the process for preparing the compound of formula 35 or a salt thereof further comprises treating the compound of formula 34 or a salt thereof with a first dealkylating agent to form the compound of formula 35 or a salt thereof. In some embodiments, the first dealkylating agent is selected from Lewis acids and nucleophilic reagents. Examples of suitable Lewis acids include, but are not limited to, boron trihalides, organoboranes, triiodides, trialkylsilyl halides, hexafluorosilicate, aluminum trihalides, lithium halides, hydrogen halides, iron trihalides, tin tetrahalides, and titanium tetrahalides. In some embodiments, the Lewis acid is selected from aluminum trichloride, boron tribromide, boron triiodide, lithium iodide, hydrogen bromide, and trimethylyl iodide (TMSI). Examples of suitable nucleophilic reagents include, but are not limited to, thiolates and 233789 36 2665047 of 99 Acta P 18 01 02928 amides, such as lithium diisopropylamide (LDA) and sodium amide (NaNH). As used herein, the term “thiol” refers to a thiol salt or thiol anion, which can be produced from a corresponding thiol by abstraction of a proton through a base. Any thiol can be used to form the thiol, for example, any alkyl thiol, including, but not limited to, propanethiols, butanethiols, pentanethiols, hexanethiols, heptanethiols, octanethiols, nonanethiols, decanethiols, undecanethiols, and dodecanethiols. In some embodiments, the thiol is dodecanethiol. In some embodiments, the base used to form the thiolate is a strong base, such as an alkali metal or alkaline earth metal hydroxide, for example, lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, calcium hydroxide, strontium hydroxide, and barium hydroxide.In some embodiments, the strong base is sodium hydroxide. In some embodiments, the first dealkylating agent is a thiolate generated using dodecanethiol and sodium hydroxide. In some embodiments, the process for preparing the compound of formula 13 further comprises preparing the compound of formula 33 or a salt thereof. In some embodiments, the process comprises treating a compound of formula A or a salt thereof with a second diboronic acid or ester in the presence of a fourth catalyst comprising a metal to form a compound of formula 32 or a salt thereof, wherein R9 represents an ester or boronic acid with the boron atom as the point of attachment to the pyrazolopyridine ring of compound 32 or a salt thereof. In some embodiments, the second ester or diboronic acid is selected from an alkenylboronic acid, an alkylboronic acid, an arylboronic acid, a heteroarylboronic acid, and a pinacol boronic ester. In some embodiments, the second ester or diboronic acid is bis(pinacolato)diboron. 233789 2665047 of 99 Minutes P 18 01 02928 In some embodiments, the fourth metal catalyst may be a nickel catalyst, a palladium catalyst, or a platinum catalyst. In some embodiments, the catalyst is a nickel catalyst. Examples of nickel catalysts include, but are not limited to, Raney nickel, supported nickel catalysts, Ponder nickel catalysts, nickel alloys, dichlorobis(tributylphosphine)nickel(II), bis(tricyclohexylphosphine)nickel(II) dichloride, tetrakis(triphenylphosphite)nickel(0), Ni(COD)2, Ni(PPh3)4, Ni(PPh3)2Cl2, Ni(acac)2, Cl2Ni(PMe3)2, Cl2Ni(PEt3)2, ChNi(Me2PPh)2, Cl2Ni(MePPh2)2, and Cl2Ni(Me2PCH2CH2PMe2). In some embodiments, the catalyst is a platinum catalyst. Examples of platinum catalysts include, but are not limited to, platinum carbonyl cyclovinylmethylsiloxane complexes, platinum divinyltetramethyldisiloxane complexes, platinum cyclovinylmethylsiloxane complexes, platinum octanaldehyde / octanol complexes, platinum olefin complexes, chloroplatinic acid olefin complexes, Karstedt's catalyst (Pt2[[(CH2=CH)(CH3)2Si]2O]3), Ashby's catalyst (Pt4[CH2=CHSi(CH3)O]4), a Lamoreaux catalyst (a Ptoctanal / octanol complex), platinum chloride, chloroplatinic acid, finely divided platinum metal (“platinum black”), platinum oxide, platinum metal on graphitized carbon, bis(acetylacetonato)platinum, (n5-cyclopentadienyl)trialkylplatinum, finely divided platinum oxide, PtO2 (“Adam's catalyst”), and chloroplatinic acid hexahydrate (Speier catalyst).In some embodiments, the catalyst is a palladium catalyst. In some embodiments, the fourth catalyst is a palladium catalyst selected from Pd(dba)2, PdCl2, Pd(OAc)2, Pd(dppf)Cl2, Pd2(dba)3, PdCl2(CH3CN)2, PdCl2(PPh3)2, Pd(t-Bu)3, Pd(dppf)CUCH2Cl2, Pd(PPh3)4, Pd(OAc) / PPh3, PdCh[(Pet3)]2, Pd(DIPHOS)2, PdCl2(Bipy), [PdCl(Ph2PCH2PPh2)]2, PdCl2[P(o-Tol)3]2, Pd2(dba)3 / P(o-Tol)3. Pd2(dba) / P(furyl)3, PdCl2[P(furyl)3]2, PdCl2(PMePh2)2, PdCl2[P(4-F-Ph)3]2, PdCl2[P(C6F6)3]2, PdCl2[P(2-COOH-Ph)(Ph)2]2, and PdCl2[P(4-COOH-Ph)(Ph)2]2. In some embodiments, the fourth catalyst comprising a metal is Pd(dppf)Cl2^CH2Cl2. In some embodiments, R9 is a boronic acid or ester. In some embodiments, the boronic acid or ester is selected from an alkenyl boronic acid, an alkyl boronic acid, an aryl boronic acid, a heteroaryl boronic acid, and a pinacol boronic ester. In some embodiments, the boronic acid or ester is the pinacol ester of boronic acid. In some embodiments, the boronic acid or ester is represented 233789 38 2665047 of 99 Acta P 18 01 02928 / T'O by the formula ' , where the wavy line indicates the point of attachment to the pyrazolo[1,5-a]pyridine ring of compound 32 or salt thereof. In some embodiments, R9 is pinacol boronic acid ester and compound 32 is compound 32a N=\ .Ñ^zA'CN AÑC BO / \ i 32a or salt of the same. In some embodiments, the process for preparing a compound of formula 33 further comprises treating the compound of formula 32 or a salt thereof with a first oxidizing agent to form the compound of formula 33 or a salt thereof. In some embodiments, the first oxidant is selected from O2, N-methylmorpholine N-oxide (NMO), chloranyl (CA), 7,7,8,8-tetracyanoquinodimethane (TCNQ), benzylidene-malononitrile (BMCN), tetracyanoethylene (TCNE), 2,3-dicyano-1,4-benzoquinone (DCBQ), and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). In some embodiments, the first oxidant is NMO. In some embodiments, the process for preparing the compound of Formula I or a pharmaceutically acceptable salt thereof further comprises preparing the compound of Formula 20 or a salt thereof. In some embodiments, the process comprises treating a compound of Formula A N=\ Pi A or a salt thereof with a second dealkylating agent to form a compound of formula 18 N^\ Ñ^zÑ^CN j I 233789 39 2665047 of 99 Act P 18 01 02928 or a salt thereof. In some embodiments, the second dealkylating agent is selected from Lewis acids and nucleophilic reagents. Examples of suitable Lewis acids include, but are not limited to, boron trihalides, organoboranes, triiodides, trialkylsilyl halides, hexafluorosilicate, aluminum trihalides, lithium halides, hydrogen halides, iron trihalides, tin tetrahalides, and titanium tetrahalides. In some embodiments, the Lewis acid is selected from aluminum trichloride, boron tribromide, boron triiodide, lithium iodide, hydrogen bromide, and trimethylyl iodide (TMSI). Examples of suitable nucleophilic reagents include, but are not limited to, thiolates and amides, such as lithium diisopropylamide (LDA) and sodium amide (NaNH₂). As used herein, the term “thiol” refers to a thiol salt or thiol anion, which can be produced from a corresponding thiol by abstraction of a proton through a base.Any thiol can be used to form the thiolate, for example, any alkyl thiol, including, but not limited to, propanethiols, butanethiols, pentanethiols, hexanethiols, heptanethiols, octanethiols, nonanethiols, decanethiols, undecanethiols, and dodecanethiols. In some embodiments, the thiol is dodecanethiol. In some embodiments, the base used to form the thiolate is a strong base, such as an alkali metal or alkaline earth metal hydroxide, for example, lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, calcium hydroxide, strontium hydroxide, and barium hydroxide. In some embodiments, the strong base is sodium hydroxide. In some embodiments, the second dealkylating agent is a thiolate generated using dodecanethiol and sodium hydroxide. In some embodiments, the process for preparing the compound of Formula I or a pharmaceutically acceptable salt thereof further comprises treating the compound of formula 18 or a salt thereof with a second triflation reagent to form a compound of formula 19 N / K or a salt thereof. 233789 2665047 of 99 Minutes P 18 01 02928 In some embodiments, the second triflation reagent is selected from N-phenyl-bis(trifluoromethanesulfonimide), N-(5-chloro-2-pyridyl)triflamide, N-(2-pyridyl)triflamide, trifluoromethanesulfonic anhydride, a trialkylsilyl triflate, and a trialkylstanyl triflate. In some embodiments, the second triflation reagent is N-phenyl-bis(trifluoromethanesulfonimide). In some embodiments, the process for preparing the compound of Formula I or a pharmaceutically acceptable salt thereof further comprises treating the compound of formula 19 or a salt thereof with a compound of formula 28 R7□,, .....¢1......or a salt thereof, wherein R7 represents an ester or boronic acid with the boron atom as the attachment point to the pyridine ring of compound 28, in the presence of a fifth catalyst comprising a metal to form a compound of formula 29 N=\ Ñ^ / Z^CN Π or a salt of the same. In some embodiments, R7 is a boronic acid or ester. In some embodiments, the boronic acid or ester is selected from an alkenyl boronic acid, an alkyl boronic acid, an aryl boronic acid, a heteroaryl boronic acid, and a pinacol boronic ester. In some embodiments, the boronic acid or ester is the pinacol ester of boronic acid. In some embodiments, the boronic acid or ester is represented by the formula ' , where the wavy line indicates the point of attachment to the pyridine ring of compound 28 or a salt thereof. In some embodiments, R7 is pinacol ester of boronic acid and compound 28 is compound 28a 233789 2665047 of 99 Minutes P 18 01 02928 In some embodiments, the fifth metal catalyst may be a nickel catalyst, a palladium catalyst, or a platinum catalyst. In some embodiments, the catalyst is a nickel catalyst. Examples of nickel catalysts include, but are not limited to, Raney nickel, supported nickel catalysts, Ponder nickel catalysts, nickel alloys, dichlorobis(tributylphosphine)nickel(II), bis(tricyclohexylphosphine)nickel(II) dichloride, tetrakis(triphenylphosphite)nickel(0), Ni(COD)2, Ni(PPh3)4, Ni(PPh3)2Cl2, Ni(acac)2, Cl2Ni(PMe3)2, Cl2Ni(PEt3)2, ChNi(Me2PPh)2, CbNi(MePPh2)2, and Cl2Ni(Me2PCH2CH2PMe2). In some embodiments, the catalyst is a platinum catalyst. Examples of platinum catalysts include, but are not limited to, platinum carbonyl cyclovinylmethylsiloxane complexes, platinum divinyltetramethyldisiloxane complexes, platinum cyclovinylmethylsiloxane complexes, platinum octanaldehyde / octanol complexes, platinum olefin complexes, chloroplatinic acid olefin complexes, Karstedt's catalyst (Pt2[[(CH2=CH)(CH3)2Si]2O]3), Ashby's catalyst (Pt4[CH2=CHSi(CH3)O]4), a Lamoreaux catalyst (a Ptoctanal / octanol complex), platinum chloride, chloroplatinic acid, finely divided platinum metal (“platinum black”), platinum oxide, platinum metal on graphitized carbon, bis(acetylacetonato)platinum, (n5-cyclopentadienyl)trialkylplatinum, finely divided platinum oxide, PtO2 (“Adam's catalyst”), and chloroplatinic acid hexahydrate (Speier catalyst).In some embodiments, the catalyst is a palladium catalyst. In some embodiments, the palladium catalyst is selected from Pd(dba)2, PdCl2, Pd(OAc)2, Pd(dppf)Cl2, Pd2(dba)3, PdCl2(CH3CN)2, PdCl2(PPh3)2, Pd(t-Bu)3. Pd(dppf)ChOH2Cl2, Pd(PPh3)4, Pd(OAc) / PPh3, PdCh[(Pet3)]2, Pd(DIPHOS)2, PdCl2(Bipy), [PdCl(Ph2PCH2PPh2)]2, PdCl2[P(o-Tol)3]2, Pd2(dba)3 / P(o-Tol)3, Pd2(dba) / P(furyl)3, PdCl2[P(furyl)3]2, PdCl2(PMePh2)2, PdCl2[P(4-F-Ph)3]2, PdCl2[P(C6F6)3]2, PdCl2[P(2-COOH-Ph)(Ph)2]2, and PdCl2[P(4-COOH-Ph)(Ph)2]2. In some embodiments, the fifth catalyst comprising a metal is Pd(dppf)Cl2^CH2Cl2. 233789 2665047 of 99 Minutes P 18 01 02928 In some embodiments, the process for preparing the compound of Formula I or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable salt thereof further comprises treating the compound of formula 29 or a salt thereof with a compound of formula 21 in the presence of 2,2-dimethyl dioxirane, a sixth catalyst comprising a metal, and a second weak base to form the compound of Formula I or a pharmaceutically acceptable salt thereof. In some embodiments, the sixth metal catalyst may be a nickel catalyst, a palladium catalyst, or a platinum catalyst. In some embodiments, the catalyst is a nickel catalyst. Examples of nickel catalysts include, but are not limited to, Raney nickel, supported nickel catalysts, Ponder nickel catalysts, nickel alloys, dichlorobis(tributylphosphine)nickel(II), bis(tricyclohexylphosphine)nickel(II) dichloride, tetrakis(triphenylphosphite)nickel(0), Ni(COD)2, Ni(PPh3)4, Ni(PPh3)2Cl2, Ni(acac)2, Cl2Ni(PMe3)2, Cl2Ni(PEt3)2, ChNi(Me2PPh)2, CbNi(MePPh2)2, and Cl2Ni(Me2PCH2CH2PMe2). In some embodiments, the catalyst is a platinum catalyst. Examples of platinum catalysts include, but are not limited to, platinum carbonyl cyclovinylmethylsiloxane complexes, platinum divinyltetramethyldisiloxane complexes, platinum cyclovinylmethylsiloxane complexes, platinum octanaldehyde / octanol complexes, platinum olefin complexes, chloroplatinic acid olefin complexes, Karstedt's catalyst (Pt2[[(CH2=CH)(CH3)2Si]2O]3), Ashby's catalyst (Pt4[CH2=CHSi(CH3)O]4), a Lamoreaux catalyst (a Ptoctanal / octanol complex), platinum chloride, chloroplatinic acid, finely divided platinum metal (“platinum black”), platinum oxide, platinum metal on graphitized carbon, bis(acetylacetonato)platinum, (n5-cyclopentadienyl)trialkylplatinum, finely divided platinum oxide, PtO2 (“Adam's catalyst”), and chloroplatinic acid hexahydrate (catalyst of 233789 43 2665047 of 99 Minutes P 18 01 02928 Speier). In some embodiments, the catalyst is a palladium catalyst. In some embodiments, the sixth catalyst is a palladium catalyst selected from Pd(dba)2, PdCh, Pd(OAc)2, Pd(dppf)Cl2, Pd2(dba)3, PdCh(CH3CN)2, PdCh(PPh3)2, Pd(t-Bu)3, Pd(dppf)Cl2OH2Cl2, Pd(PPh3)4, Pd(OAc) / PPh3, PdCb[(Pet3)]2, Pd(DIPHOS)2, PdCl2(Bipy), [PdCl(Ph2PCH2PPh2)]2, PdCl2[P(o-Tol)3]2, Pd2(dba)3 / P(o-Tol)3, Pd2(dba) / P(furyl)3, PdCl2[P(furyl)3]2, PdCl2(PMePh2)2, PdCl2[P(4-F-Ph)3]2, PdCl2[P(C6F6)3]2, PdCl2[P(2-COOH-Ph)(Ph)2]2, and PdCl2[P(4-COOH-Ph)(Ph)2]2. In some embodiments, the sixth catalyst comprising a metal is Pd2(dba)3. In some embodiments, the second weak base is selected from a carbonate, a bicarbonate, methylamine, ammonia, trimethylammonia, pyridine, and aniline. Examples of carbonates include, but are not limited to, calcium carbonate, lithium carbonate, sodium carbonate, potassium carbonate, and cesium carbonate. Examples of bicarbonates include, but are not limited to, sodium bicarbonate, potassium bicarbonate, cesium bicarbonate, magnesium bicarbonate, calcium bicarbonate, and ammonium bicarbonate. In some embodiments, the second weak base is cesium carbonate (Cs₂CO₃). In some embodiments, the process for preparing the compound of Formula I or a pharmaceutically acceptable salt thereof comprises treating a compound of formula 29 or a salt thereof with a third ester or diboronic acid in the presence of a seventh catalyst comprising a metal to form a compound of formula 30 or a salt thereof, wherein R8 represents an ester or boronic acid with the boron atom as the point of attachment to the pyrazolopyridine ring of compound 30 or a salt thereof. In some embodiments, the third boronic acid or ester is selected from an alkenyl boronic acid, an alkyl boronic acid, an aryl boronic acid, a heteroaryl boronic acid, and a pinacol boronic ester. In some embodiments, the third boronic acid or ester is bis(pinacolato)diboron. 233789 2665047 of 99 Minutes P 18 01 02928 In some embodiments, the seventh metal catalyst may be a nickel catalyst, a palladium catalyst, or a platinum catalyst. In some embodiments, the catalyst is a nickel catalyst. Examples of nickel catalysts include, but are not limited to, Raney nickel, supported nickel catalysts, Ponder nickel catalysts, nickel alloys, dichlorobis(tributylphosphine)nickel(II), bis(tricyclohexylphosphine)nickel(II) dichloride, tetrakis(triphenylphosphite)nickel(0), Ni(COD)2, Ni(PPh3)4, Ni(PPh3)2Cl2, Ni(acac)2, Cl2Ni(PMe3)2, Cl2Ni(PEt3)2, ChNi(Me2PPh)2, Cl2Ni(MePPh2)2, and Cl2Ni(Me2PCH2CH2PMe2). In some embodiments, the catalyst is a platinum catalyst. Examples of platinum catalysts include, but are not limited to, platinum carbonyl cyclovinylmethylsiloxane complexes, platinum divinyltetramethyldisiloxane complexes, platinum cyclovinylmethylsiloxane complexes, platinum octanaldehyde / octanol complexes, platinum olefin complexes, chloroplatinic acid olefin complexes, Karstedt's catalyst (Pt2[[(CH2=CH)(CH3)2Si]2O]3), Ashby's catalyst (Pt4[CH2=CHSi(CH3)O]4), a Lamoreaux catalyst (a Ptoctanal / octanol complex), platinum chloride, chloroplatinic acid, finely divided platinum metal (“platinum black”), platinum oxide, platinum metal on graphitized carbon, bis(acetylacetonato)platinum, (n5-cyclopentadienyl)trialkylplatinum, finely divided platinum oxide, PtO2 (“Adam's catalyst”), and chloroplatinic acid hexahydrate (Speier catalyst).In some embodiments, the catalyst is a palladium catalyst. In some embodiments, the seventh catalyst is a palladium catalyst selected from Pd(dba)2, PdCl2, Pd(OAc)2, Pd(dppf)Cl2, Pd2(dba)3, PdCl2(CH3CN)2, PdCl2(PPh3)2, Pd(t-Bu)3, Pd(dppf)Ch-CH2Cl2, Pd(PPh3)4, Pd(OAc) / PPh3, PdCh[(Pet3)]2, Pd(DIPHOS)2, PdCl2(Bipy), [PdCl(Ph2PCH2PPh2)]2, PdCl2[P(o-Tol)3]2, Pd2(dba)3 / P(oTol)3, Pd2(dba) / P(furyl)3, PdCl2[P(furyl)3]2, PdCl2(PMePh2)2, PdCl2[P(4-F-Ph)3]2, PdCl2[P(C6F6)3]2, PdCl2[P(2-COOH-Ph)(Ph)2]2, and PdCl2[P(4-COOH-Ph)(Ph)2]2. In some embodiments, the seventh catalyst comprising a metal is Pd(dppf)ChOH2Cl2. In some embodiments, R8 is a boronic acid or ester. In some embodiments, the boronic acid or ester is selected from an alkenyl boronic acid, an alkyl boronic acid, an aryl boronic acid, a heteroaryl boronic acid, and a pinacol boronic ester. In some embodiments, the boronic acid or ester is the pinacol ester of boronic acid. In some embodiments, the boronic acid or ester is represented as 233789 45 2665047 of 99 Act P 18 01 02928 by the formula ' , where the wavy line indicates the point of attachment to the pyridine ring of compound 30 or salt thereof. In some embodiments, R8 is pinacol ester of boronic acid and compound is compound 30a or get out of it. In some embodiments, the process for preparing the compound of Formula I or a pharmaceutically acceptable salt thereof further comprises treating the compound of formula 30 or a salt thereof with a fourth strong base and hydrogen peroxide to form a compound of formula 31 or a salt of it. In some embodiments, the fourth strong base is an alkali metal or alkaline earth metal hydroxide. For example, the fourth strong base is selected from lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, calcium hydroxide, strontium hydroxide, and barium hydroxide. In some embodiments, the fourth strong base is sodium hydroxide. In some embodiments, the process for preparing the compound of Formula I or a pharmaceutically acceptable salt thereof further comprises treating the compound of formula 31 or a salt thereof with 2,2-dimethyloxirane in the presence of a fifth strong base to form the compound of Formula I or a pharmaceutically acceptable salt thereof. 233789 46 2665047 of 99 Minutes P 18 01 02928 In some embodiments, the fifth strong base is an alkali metal or alkaline earth metal hydroxide. For example, the fifth strong base is selected from lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, calcium hydroxide, strontium hydroxide, and barium hydroxide. In some embodiments, the fifth strong base is sodium hydroxide. In some embodiments, the process for preparing the compound of Formula I or a pharmaceutically acceptable salt thereof further comprises treating the compound of formula 19 or a salt thereof with a compound of formula 12 or a salt thereof, wherein X represents a halogen or a sulfonate and R6 represents an ester or boronic acid with the boron atom as the attachment point to the pyridine ring of compound 12, in the presence of an eighth catalyst comprising a metal to form the compound of formula 20 or a salt thereof. In some embodiments, X is a halogen or a sulfonate. For example, X is selected from the group consisting of F, Cl, Br, and I. In some embodiments, X is F. In some embodiments, X is a sulfonate. For example, X is selected from the group consisting of triflate, mesylate, and tosylate. In some embodiments, R6 is an ester or boronic acid. In some embodiments, the ester or boronic acid is pinacol, the ester of boronic acid. In some / 7Ό embodiments, the ester or boronic acid is represented by the formula / , where the wavy line indicates the point of attachment to the pyridine ring of compound 12 or a salt thereof. In some embodiments, R6 is pinacol boronic acid ester and compound 12 is compound 12a / =N T / )—F 12a or salt of it. 233789 2665047 of 99 Minutes P 18 01 02928 In some embodiments, the eighth metal catalyst may be a nickel catalyst, a palladium catalyst, or a platinum catalyst. In some embodiments, the catalyst is a nickel catalyst. Examples of nickel catalysts include, but are not limited to, Raney nickel, supported nickel catalysts, Ponder nickel catalysts, nickel alloys, dichlorobis(tributylphosphine)nickel(II), bis(tricyclohexylphosphine)nickel(II) dichloride, tetrakis(triphenylphosphite)nickel(0), Ni(COD)2, Ni(PPh3)4, Ni(PPh3)2Cl2, Ni(acac)2, Cl2Ni(PMe3)2, Cl2Ni(PEt3)2, ChNi(Me2PPh)2, CbNi(MePPh2)2, and Cl2Ni(Me2PCH2CH2PMe2). In some embodiments, the catalyst is a platinum catalyst. Examples of platinum catalysts include, but are not limited to, platinum carbonyl cyclovinylmethylsiloxane complexes, platinum divinyltetramethyldisiloxane complexes, platinum cyclovinylmethylsiloxane complexes, platinum octanaldehyde / octanol complexes, platinum olefin complexes, chloroplatinic acid olefin complexes, Karstedt's catalyst (Pt2[[(CH2=CH)(CH3)2Si]2O]3), Ashby's catalyst (Pt4[CH2=CHSi(CH3)O]4), a Lamoreaux catalyst (a Ptoctanal / octanol complex), platinum chloride, chloroplatinic acid, finely divided platinum metal (“platinum black”), platinum oxide, platinum metal on graphitized carbon, bis(acetylacetonato)platinum, (n5-cyclopentadienyl)trialkylplatinum, finely divided platinum oxide, PtO2 (“Adam's catalyst”), and chloroplatinic acid hexahydrate (Speier catalyst).In some embodiments, the catalyst is a palladium catalyst. In some embodiments, the palladium catalyst is selected from Pd(dba)2, PdCl2, Pd(OAc)2, Pd(dppf)Cl2, Pd2(dba)3, PdCl2(CH3CN)2, PdCl2(PPh3)2, Pd(t-Bu)3. Pd(dppf)CUCH2Cl2, Pd(PPh3)4, Pd(OAc) / PPh3, PdCh[(Pet3)]2, Pd(DIPHOS)2, PdCl2(Bipy), [PdCl(Ph2PCH2PPh2)]2, PdCl2[P(o-Tol)3]2, Pd2(dba)3 / P(o-Tol)3, Pd2(dba) / P(furyl)3, PdCl2[P(furyl)3]2, PdCl2(PMePh2)2, PdCl2[P(4-F-Ph)3]2, PdCl2[P(C6F6)3]2, PdCl2[P(2-COOH-Ph)(Ph)2]2, and PdCl2[P(4-COOH-Ph)(Ph)2]2. In some embodiments, the eighth catalyst comprising a metal is Pd(dppf)Cl2^CH2Cl2. In some embodiments, a process is provided herein for preparing a compound of formula 15 233789 2665047 of 99 Minutes P 18 01 02928 or a salt thereof, wherein R1 is an amine protecting group. In some embodiments, the process for preparing the compound of formula or a salt thereof comprises treating a compound of formula 26 or a salt thereof, wherein R1 is an amine protecting group, with 2,2-dimethyloxirane in the presence of a sixth strong base to form the compound of formula 15 or a salt thereof. In some embodiments, R1 is an amine protecting group selected from formyl, acetyl, trifluoroacetyl, benzyl, benzoyl, carbamate, benzyloxycarbonyl, p-methoxybenzyl carbonyl, tert-butyloxycarbonyl (Boc), trimethylsilyl, 2-trimethylsilylethanesulfonyl, trityl and substituted trityl groups, allyloxycarbonyl, 9-fluorenylmethyloxycarbonyl, nitroveratryloxycarbonyl, p-methoxybenzyl, and tosyl. In some embodiments, R1 is tert-butyloxycarbonyl (Boc). In some embodiments, the sixth strong base is selected from lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, calcium hydroxide, strontium hydroxide, and barium hydroxide. In some embodiments, the sixth strong base is potassium hydroxide. In some embodiments, the process for preparing the compound of Formula I or a pharmaceutically acceptable salt thereof further comprises preparing the compound of Formula 26 or a salt thereof. In some embodiments, the process comprises treating a compound of Formula B 233789 2665047 of 99 Minutes P 18 01 02928 or a salt thereof with a compound of formula 24r,-Q-nSn-rio, wherein R1 is an amine protecting group and R3 represents an ester or boronic acid with the boron atom as the attachment point to the pyridine ring of compound 24, in the presence of a ninth catalyst comprising a metal to form a compound of formula 25 or a salt of it. In some embodiments, R1 is an amine protecting group selected from formyl, acetyl, trifluoroacetyl, benzyl, benzoyl, carbamate, benzyloxycarbonyl, p-methoxybenzyl carbonyl, tert-butyloxycarbonyl (Boc), trimethylsilyl, 2-trimethylsilylethanesulfonyl, trityl and substituted trityl groups, allyloxycarbonyl, 9-fluorenylmethyloxycarbonyl, nitroveratryloxycarbonyl, p-methoxybenzyl, and tosyl. In some embodiments, R1 is tert-butyloxycarbonyl (Boc). In some embodiments, R3 is a boronic acid or ester. In some embodiments, the boronic acid or ester is selected from an alkenyl boronic acid, an alkyl boronic acid, an aryl boronic acid, a heteroaryl boronic acid, and a pinacol boronic acid ester. In some embodiments, the boronic acid or ester is the pinacol ester of boronic acid. In some embodiments, the boronic acid or ester is represented 233789 2665047 of 99 Acta P 18 01 02928 / T'O by the formula ' , where the wavy line indicates the point of attachment to the pyridine ring of compound 24 or salt thereof. In some embodiments, R1 is Boc and R3 is pinacol boronic acid ester and compound 24 is compound 24a B-(\ / )—N < N-Boc 24a or salt of it. In some embodiments, R1es Boc and compound 25 is compound 25a 25a or salt of it. In some embodiments, the ninth catalyst comprising a metal may be a nickel catalyst, a palladium catalyst, or a platinum catalyst. In some embodiments, the catalyst is a nickel catalyst. Examples of nickel catalysts include, but are not limited to, Raney nickel, supported nickel catalysts, Ponder nickel catalysts, nickel alloys, dichlorobis(tributylphosphine)nickel(II), bis(tricyclohexylphosphine)nickel(II) dichloride, tetrakis(triphenylphosphite)nickel(0), Ni(COD)2, Ni(PPh3)4, Ni(PPh3)2Cl2, Ni(acac)2, Cl2Ni(PMe3)2, Cl2Ni(PEt3)2, ChNi(Me2PPh)2, CbNi(MePPh2)2, and Cl2Ni(Me2PCH2CH2PMe2). In some embodiments, the catalyst is a platinum catalyst. Examples of platinum catalysts include, but are not limited to, platinum carbonyl cyclovinylmethylsiloxane complexes, platinum divinyltetramethyldisiloxane complexes, platinum cyclovinylmethylsiloxane complexes, platinum octanaldehyde / octanol complexes, platinum olefin complexes, chloroplatinic acid olefin complexes, Karstedt's catalyst (Pt2[[(CH2=CH)(CH3)2Si]2O]3), Ashby's catalyst (Pt4[CH2=CHSi(CH3)O]4), and a Lamoreaux catalyst (a Pt233789 complex). 2665047 of 99 Acta P 18 01 02928 octanal / octanol), platinic chloride, chloroplatinic acid, finely divided platinum metal (“platinum black”), platinum oxide, platinum metal on graphitized carbon, bis(acetylacetonato)platinum, (n5-cyclopentadienyl)trialkylplatinum, finely divided platinum oxide, PtO2 (“Adam’s catalyst”), and chloroplatinic acid hexahydrate (Speier’s catalyst). In some embodiments, the catalyst is a palladium catalyst. In some embodiments, the palladium catalyst is selected from Pd(dba)2, PdCl2, Pd(OAc)2, Pd(dppf)Cl2, Pd2(dba)3, PdCh(CH3CN)2, PdCh(PPh3)2, Pd(t-Bu)3, Pd(dppf)ChOH2Cl2, Pd(PPh3)4, Pd(OAc) / PPh3, PdCh[(Pet3)]2, Pd(DIPHOS)2, PdCl2(Bipy), [PdCl(Ph2PCH2PPh2)]2, PdCl2[P(o-Tol)3]2, Pd2(dba)3 / P(o-Tol)3, Pd2(dba) / P(furyl)3, PdCl2[P(furyl)3]2, PdCl2(PMePh2)2, PdCl2[P(4-F-Ph)3]2, PdCl2[P(C6F6)3]2, PdCl2[P(2-COOH-Ph)(Ph)2]2, and PdCl2[P(4-COOH-Ph)(Ph)2]2. In some embodiments, the ninth catalyst comprising a metal is Pd(dppf)ChOH2Cl2. In some embodiments, the process for preparing the compound of Formula I or a pharmaceutically acceptable salt thereof further comprises treating the compound of formula 25 or a salt thereof with a fourth ester or diboronic acid in the presence of a tenth catalyst comprising a metal to form a mixture, and treating the mixture with a seventh strong base and hydrogen peroxide to form the compound of formula 26 or a salt thereof. In some embodiments, the tenth metal catalyst may be a nickel catalyst, a palladium catalyst, or a platinum catalyst. In some embodiments, the catalyst is a nickel catalyst. Examples of nickel catalysts include, but are not limited to, Raney nickel, supported nickel catalysts, Ponder nickel catalysts, nickel alloys, dichlorobis(tributylphosphine)nickel(II), bis(tricyclohexylphosphine)nickel(II) dichloride, tetrakis(triphenylphosphite)nickel(0), Ni(COD)2, Ni(PPh3)4, Ni(PPh3)2Cl2, Ni(acac)2, Cl2Ni(PMe3)2, Cl2Ni(PEt3)2, Cl2Ni(Me2PPh)2, Cl2Ni(MePPh2)2, and Cl2Ni(Me2PCH2CH2PMe2). In some embodiments, the catalyst is a platinum catalyst. Examples of platinum catalysts include, but are not limited to, platinum carbonyl cyclovinylmethylsiloxane complexes, platinum divinyltetramethyldisiloxane complexes, platinum cyclovinylmethylsiloxane complexes, platinum octanaldehyde / octanol complexes, platinum olefin complexes, chloroplatinic acid olefin complexes, Karstedt catalyst (Pt2[[(CH2=CH)(CH3)2Si]2O]3), and other catalysts. 233789 2665047 of 99 Minutes P 18 01 02928 Ashby (Pt4[CH2=CHSi(CH3)O]4), a Lamoreaux catalyst (a Ptoctanal / octanol complex), platinum chloride, chloroplatinic acid, finely divided platinum metal (“platinum black”), platinum oxide, platinum metal on graphitized carbon, bis(acetylacetonato)platinum, (n5-cyclopentadienyl)trialkylplatinum, finely divided platinum oxide, PtO2 (“Adam catalyst”), and chloroplatinic acid hexahydrate (Speier catalyst). In some embodiments, the catalyst is a palladium catalyst. In some embodiments, the palladium catalyst is selected from Pd(dba)2, PdCl2, Pd(OAc)2, Pd(dppf)Cl2, Pd2(dba)3, PdCl2(CH3CN)2, PdCl2(PPh3)2, Pd(t-Bu)3, Pd(dppf)Cl2^CH2Cl2, Pd(PPh3)4, Pd(OAc) / PPh3, PdCb[(Pet3)]2, Pd(DIPHOS)2, PdCl2(Bipy), [PdCl(Ph2PCH2PPh2)]2, PdCl2[P(o-Tol)3]2, Pd2(dba)3 / P(o-Tol)3, Pd2(dba) / P(furyl)3, PdCl2[P(furyl)3]2, PdCl2(PMePh2)2, PdCl2[P(4-F-Ph)3]2, PdCl2[P(C6F6)3]2, PdCl2[P(2-COOH-Ph)(Ph)2]2, and PdCl2[P(4-COOH-Ph)(Ph)2]2. In some embodiments, the tenth catalyst comprising a metal is Pd(dbbf). In some embodiments, the fourth ester or diboronic acid is selected from an alkenylboronic acid, an alkylboronic acid, an arylboronic acid, a heteroarylboronic acid, and a pinacol boronic ester. In some embodiments, the fourth ester or diboronic acid is bis(pinacolato)diboron. In some embodiments, the seventh strong base is selected from lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, calcium hydroxide, strontium hydroxide, and barium hydroxide. In some embodiments, the seventh strong base is sodium hydroxide. In some embodiments, the seventh strong base is 1.0 M sodium hydroxide. In some embodiments, R1 is Boc and compound 26 is compound 26a 26a or salt of it. In some embodiments, a compound of formula 13 or a salt thereof can be prepared as shown in Scheme 1, wherein X, R2 and R5 are defined below. 233789 2665047 of 99 Minutes P 18 01 02928 Scheme 1 In some embodiments, X is selected from a halogen and a sulfonate. In some embodiments, X is selected from the group consisting of F, Cl, Br, 5, and I. In some embodiments, X is F. In some embodiments, X is a sulfonate. In some embodiments, X is selected from the group consisting of triflate, mesylate, and tosylate. In some embodiments of Scheme 1, R2 is selected from the group consisting of an organoborane compound, an organostane compound represented by the formula -Sn(alkyl)3, a zinc halide represented by the formula -ZnX, where X is a halide, and a magnesium halide represented by the formula -MgX, where X is a halide. In some embodiments, R2 is an organoborane compound. In some embodiments, R2 is an ester or boronic acid. In some embodiments, the ester or boronic acid is pinacol ester of boronic acid. In some embodiments, the ester or boronic acid is represented by the formula / , where the wavy line indicates the point of attachment to the pyridine ring of compound 12 or a salt thereof. 233789 2665047 of 99 Minutes P 18 01 02928 In some embodiments, R2 is pinacol boronic acid ester and compound 12 is compound 12a 12a or salt of it. In some embodiments of Scheme 1, R5 is a boronic acid or ester. In some embodiments, the boronic acid or ester is selected from an alkenyl boronic acid, an alkyl boronic acid, an aryl boronic acid, a heteroaryl boronic acid, and a pinacol boronic ester. In some embodiments, the boronic acid or ester is a pinacol ester of boronic acid. In some embodiments, the boronic acid or ester is represented by the formula where the wavy line indicates the point of attachment to the pyrazolo[1,5-a]pyridine ring of compound 22 or a salt thereof. In some embodiments, the compound of formula 13 or a salt thereof can be prepared as shown in scheme 2, wherein X, R6 and R9 are defined below. 233789 2665047 of 99 Minutes P 18 01 02928 In some embodiments of Scheme 2, X is selected from a halogen and a sulfonate. In some embodiments, X is selected from the group consisting of F, Cl, Br, and I. In some embodiments, X is F. In some embodiments, X is a sulfonate. In some embodiments, X is selected from the group consisting of triflate, mesylate, and tosylate. In some embodiments of Scheme 2, R6 is an ester or boronic acid. In some embodiments, the ester or boronic acid is pinacol, the ester of boronic acid. In some embodiments, the ester or boronic acid is represented by the formula Vn / ' / ''O / , where the wavy line indicates the point of attachment to the pyridine ring of compound 12 or a salt thereof. In some embodiments of Scheme 2, R9 is a boronic acid or ester. In some embodiments, the boronic acid or ester is selected from an alkenyl boronic acid, an alkyl boronic acid, an aryl boronic acid, a heteroaryl boronic acid, and a pinacol boronic acid ester. In some embodiments, the diboroic acid or ester is the pinacol ester of boronic acid. In some embodiments, the boronic acid or ester / / O is represented by the formula , , where the wavy line indicates the point of attachment to the pyrazolo[1,5-a]pyridine ring of compound 32 or a salt thereof. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof can be prepared as shown in Scheme 3, wherein X and R1 are defined below. 233789 2665047 of 99 Minutes P 18 01 02928 In some embodiments of Scheme 3, X is selected from a halogen and a sulfonate. In some embodiments, X is selected from the group consisting of F, Cl, Br, and I. In some embodiments, X is F. In some embodiments, X is a sulfonate. In some embodiments, X is selected from the group consisting of triflate, mesylate, and tosylate. In some embodiments of Scheme 3, R1 is an amine protecting group selected from formyl, acetyl, trifluoroacetyl, benzyl, benzoyl, carbamate, 10-benzyloxycarbonyl, p-methoxybenzyl carbonyl, tert-butyloxycarbonyl (Boc), trimethylsilyl, 2-trimethylsilylethanesulfonyl, trityl and substituted trityl groups, allyloxycarbonyl, 9-fluorenylmethyloxycarbonyl, nitroveratryloxycarbonyl, p-methoxybenzyl, and tosyl. In some embodiments, R1 is tert-butyloxycarbonyl (Boc). In some embodiments, R1es Boc and compound 14 is compound 14a Boc Yo H 14a or salt of it. 233789 2665047 of 99 Minutes P 18 01 02928 In some embodiments, R1es Boc and compound 15 is compound 15a or get out of it. In some embodiments, R1 is Boc and compound 26 is compound 26a 26a or salt of it. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt 10 thereof can be prepared as shown in Scheme 4, wherein R7 is defined as follows. 233789 2665047 of 99 Minutes P 18 01 02928 In some embodiments of Scheme 4, R7 is a boronic acid or ester. In some embodiments, the boronic acid or ester is selected from an alkenyl boronic acid, an alkyl boronic acid, an aryl boronic acid, a heteroaryl boronic acid, and a pinacol boronic ester. In some embodiments, the diboroic acid or ester is the pinacol ester of boronic acid. In some embodiments, the boronic acid or ester / 7~O is represented by the formula ' , where the wavy line indicates the point of attachment to the pyridine ring of compound 28 or a salt thereof. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof can be prepared as shown in Scheme 5, wherein R8 is defined as follows. 233789 2665047 of 99 Minutes P 18 01 02928 Scheme 5 In some embodiments of Scheme 5, R8 is a boronic acid or ester. In some embodiments, the boronic acid or ester is selected from an alkenyl boronic acid, an alkyl boronic acid, an aryl boronic acid, a heteroaryl boronic acid, and a pinacol boronic ester. In some embodiments, the diboroic acid or ester is the pinacol ester of boronic acid. In some embodiments, the boronic acid or ester / 7^0 is represented by the formula / , where the wavy line indicates the point of attachment to the pyridine ring of compound 30 or a salt thereof. In some embodiments, the compound of formula 20 or a salt thereof can be prepared as shown in scheme 6, wherein R6 is defined as follows. Scheme 6 In some embodiments of Scheme 6, R6 is an ester or boronic acid. In some embodiments, the ester or boronic acid is pinacol, the ester of boronic acid. 233789 2665047 of 99 Minutes P 18 01 02928 In some embodiments, the ester or boronic acid is represented by the formula / T'-o / , where the wavy line indicates the point of attachment to the pyridine ring of compound 12 or salt thereof. In some embodiments, the process further comprises preparing the compound of formula A or a salt thereof by a process comprising: a) treat a compound of formula 1a or a salt thereof with O-(mesethylsulfonyl)hydroxylamine to form a compound of formula 2a b) treating the compound of formula 2a with acrylonitrile or an acrylonitrile derivative in the presence of a first non-nucleophilic base to form the compound of formula A. In some embodiments, the compound of formula A or a salt thereof is prepared by a process comprising: a) treat a compound of formula 1a 1a or a salt thereof with O-(mesethylsulfonyl)hydroxylamine to form a compound of formula 2a b) treat the compound of formula 2a with a compound of formula 27 233789 2665047 of 99 Minutes P 18 01 02928 EITHER or a salt thereof, wherein R4 is a C1-C6 alkyl, to form a mixture of the compounds of formula 3 and formula 4 or you leave it; c) separate the compound of formula 3 from the compound of formula 4; d) treat the compound of formula 3 with a first dilute strong acid to form a compound of formula 5A or a salt of it; e) treating the compound of formula 5A or a salt thereof with a first substituted amide and a first acid chloride to form a compound of formula 6A 6A or a salt thereof; f) treating the compound of formula 6A or a salt thereof with hydroxylamine to form a compound of formula 7A 7A or a salt thereof; and 233789 2665047 of 99 Minutes P 18 01 02928 g) treat the compound of formula 7A with a first acid anhydride to form the compound of formula A. In some embodiments, a compound of formula A or a salt thereof can be prepared as shown in scheme 7, wherein R4 is defined as follows 5. Scheme 7 In some embodiments of Scheme 7, R4 is a C1-C6 alkyl group selected from methyl, ethyl, propyl, butyl, pentyl, and hexyl. In some embodiments, the C1-C6 alkyl group is a straight-chain alkyl group. In some embodiments, the C1-C6 alkyl group is branched. In some embodiments, the C1-C6 alkyl group is methyl. In some embodiments, the C1-C6 alkyl group is ethyl. In some embodiments, R4 is ethyl and compound 27 is compound 27a or 27a or salt of the same. In some embodiments, R4 is ethyl and compound 3 is compound 3a 233789 2665047 of 99 Minutes P 18 01 02928 or get out of it. In some embodiments, R4 is ethyl and compound 4 is compound 4a or get out of it. In some embodiments, the compound of formula 2a or a salt thereof is treated with acrylonitrile or an acrylonitrile derivative. In some embodiments, the acrylonitrile derivative is 2-chloroacrylonitrile. In some embodiments, the compound of formula 2 or a salt thereof is treated with CH2=C(Y)CN, where Y is hydrogen or a labile group. In some embodiments, Y is a halogen. For example, Y is selected from the group consisting of F, Cl, Br, and I. In some embodiments, Y is Cl. In some embodiments, the compound of formula 2a or a salt thereof is treated with acrylonitrile or an acrylonitrile derivative in the presence of a first non-nucleophilic base. In some embodiments, the first non-nucleophilic base is selected from triethylamine (TEA), diisopropylethylamine (DIPEA), N-methylmorpholine (NMM), tri-tert-butylpyrimidine (TTBP), 1,4-diazabicyclo-[2,2,2]octane (DABCO), 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU), N,N-diethylaniline, pyridine, 2,6-lutidine, 2,4,6-collidine, 4-dimethylaminopyridine, quinuclidine, 2,6-di-tert-butylpyridine, tert-butylphosphacene, lithium diisopropylamide, sodium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, lithium tetramethylpiperidide, sodium hydride, potassium hydride, sodium tert-butoxide, and potassium tert-butoxide. In some embodiments, the first non-nucleophilic base is DBU. In some embodiments, the compound of formula 3 or a salt thereof is treated with a first dilute strong acid. In some embodiments, the first dilute strong acid is selected from perchloric acid, hydroiodic acid, hydrobromic acid, or other acids. 233789 2665047 of 99 Acta P 18 01 02928 hydrochloric acid, sulfuric acid, p-toluenesulfonic acid, and methanesulfonic acid. In some embodiments, the first dilute strong acid is dilute hydrobromic acid. In some embodiments, the compound of formula 5A or a salt thereof is treated with a first substituted amide. As used herein, the term “substituted amide” refers to an amide group having a set of its hydrogen atoms replaced by a set of substituent groups. Examples of N-substituted amide groups include -(C=O)NRR', where R and R' are independently selected from hydride groups, alkyl groups, alkenyl groups, alkynyl groups, and aryl groups, and at least one of R and R' is not a hydride group. In some embodiments, the first substituted amide is selected from benzyl methylformamide, N-formylmorpholine, dimethylacetamide, N-methylpyrrolidone, N-methylformanilide, N,N-dimethylformamide (DMF), N-methylformamide, N-formylpiperidine, and N-formylindoline. In some embodiments, the first substituted amide is DMF. In some embodiments, the compound of formula 5A or a salt thereof is treated with a first acid chloride. In some embodiments, the first acid chloride is selected from phosphoryl chloride (POCl3), phosgene (COCl2), thionyl chloride (SOCl2), oxalyl chloride (C2O2Cl2), acetyl chloride (CH3COCl), an aromatic acid chloride (ArCOCl), an aromatic thionyl chloride (ArSO2Cl), phosphorus pentachloride (PCl5), dimethylsulfamoyl chloride (Me2NSO2Cl), and dialkoxysulfamoyl chloride (RO2CNHSO2Cl). In some embodiments, the first acid chloride is POCl3. In some embodiments, the compound of formula 7A or a salt thereof is treated with a first acid anhydride. In some embodiments, the first acid anhydride is selected from acetic anhydride, formic anhydride, propionic anhydride, butyric anhydride, succinic anhydride, glutaric anhydride, methylsuccinic anhydride, maleic anhydride, methylmaleic anhydride, phthalic anhydride, 1,2,3,6-tetrahydrophthalic anhydride, 3,4,5,6-tetrahydrophthalic anhydride, hexahydrophthalic anhydride, cis-5-norbornene-(endo, exo)-2,3-dicarboxylic anhydride, and mixtures thereof. In some embodiments, the first acid anhydride is acetic anhydride. In some embodiments, the process further comprises preparing the compound of formula A or a salt thereof by a process comprising: a) treat a compound of formula 8A 233789 2665047 of 99 Minutes P 18 01 02928 N. LA 8A or a salt thereof with O-(2,4-dinitrophenyl)hydroxylamine to form the compound of formula 9A 9A; and b) treating the compound of formula 9A with acrylonitrile or an acrylonitrile derivative in the presence of a first non-nucleophilic base to form the compound of formula A. In some embodiments, the compound of formula 9A is treated with acrylonitrile or an acrylonitrile derivative that is 2-chloroacrylonitrile. In some embodiments, the first non-nucleophilic base is selected from triethylamine (TEA), diisopropylethylamine (DIPEA), N-methylmorpholine (NMM), tri-tert-butylpyrimidine (TTBP), 1,4-diazabicyclo-[2,2,2]octane (DABCO), 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU), N,N-diethylaniline, pyridine, 2,6-lutidine, 2,4,6-collidine, 4-dimethylaminopyridine, quinuclidine, 2,6-di-tert-butylpyridine, tert-butylphosphacene, lithium diisopropylamide, sodium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, lithium tetramethylpiperidide, sodium hydride, potassium hydride, sodium tert-butoxide, and potassium tert-butoxide. In some embodiments, the first non-nucleophilic base is DBU. In some embodiments, a compound of formula A or a salt thereof can be prepared as shown in scheme 11. Scheme 11 N O2N YH2 °2N. f ¡1 .N © / =\ n H2N-O—G >NO2J ® 1 °—A / ΗNO2 Br OMezA / / Δv__V a) Brom OMe b) where X is a halogen. 233789 2665047 of 99 Minutes P 18 01 02928 In some embodiments of Scheme 11, the intermediate 1-amino-3-bromo-5-methoxypyridin-1-ium 2,4dinitrophenolate (9A) formed in (a) is isolated before the cyclization step (b). In some embodiments, a compound of formula A or a salt thereof can be prepared as shown in scheme 12 Scheme 12 where X is a halogen. In scheme 12, the intermediate 1-amino-3-bromo-510 methoxypyridin-1-ium 2,4-dinitrophenolate (9A) formed is not isolated before the cyclization step. In some embodiments, a compound of formula A or a salt thereof can be prepared as shown in scheme 13. Scheme 13 In some embodiments of Scheme 13, the intermediate 1-amino-3-bromo-5-methoxypyridin-1-ium 2,4dinitrophenolate (9A) formed in (a) is isolated before the cyclization step (b). 233789 2665047 of 99 Minutes P 18 01 02928 In some embodiments, a compound of formula A or a salt thereof can be prepared as shown in Scheme 14 Scheme 14 In scheme 14, the intermediate 1-amino-3-bromo-5-methoxypyridin-1-ium 2,4-dinitrophenolate (9A) formed is not isolated before the cyclization step. In some embodiments, a compound of formula 26 or a salt thereof can be prepared as shown in scheme 8, wherein R1 and R3 are as defined below. Scheme 8 In some embodiments of Scheme 8, R1 is an amine protecting group selected from formyl, acetyl, trifluoroacetyl, benzyl, benzoyl, carbamate, benzyloxycarbonyl, p-methoxybenzyl carbonyl, tert-butyloxycarbonyl (Boc), trimethylsilyl, 2-trimethylsilylethanesulfonyl, trityl and substituted trityl groups, allyloxycarbonyl, 9-fluorenylmethyloxycarbonyl, nitroveratryloxycarbonyl, p-methoxybenzyl, and tosyl. In some embodiments, R1 is tert-butyloxycarbonyl (Boc). In some embodiments of Scheme 8, R3 is an ester or boronic acid. In some embodiments, the ester or boronic acid is selected from an alkenyl boronic acid, an alkyl boronic acid, an aryl boronic acid, a heteroaryl boronic acid, and 233789 2665047 of 99 Acta P 18 01 02928 a pinacol boronic ester. In some embodiments, the ester or diboroic acid is a pinacol ester of boronic acid. In some embodiments, the ester or boronic acid / / O is represented by the formula / , where the wavy line indicates the point of attachment to the pyridine ring of compound 24 or a salt thereof. In some embodiments, the process further comprises preparing the compound of formula B or a salt thereof by a process comprising: a) treat a compound of formula 8 or a salt thereof with O-(mesethylsulfonyl)hydroxylamine to form the compound of formula 9 9; and b) treating the compound of formula 9 with acrylonitrile or an acrylonitrile derivative in the presence of a second non-nucleophilic base to form a mixture, and treating the mixture with a second oxidant to form the compound of formula B. In some embodiments, a compound of formula B or a salt thereof can be prepared as shown in scheme 9. Scheme 9 89 B In some embodiments, the compound of formula 9 is treated with acrylonitrile or an acrylonitrile derivative that is 2-chloroacrylonitrile. In some embodiments, the second non-nucleophilic base is selected from triethylamine (TEA), diisopropylethylamine (DIPEA), N-methylmorpholine (NMM), tri-ter233789 2665047 of 99 Acta P 18 01 02928 butylpyrimidine (TTBP), 1,4-diazabicyclo-[2,2,2]octane (DABCO), 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU), N,N-diethylaniline, pyridine, 2,6-lutidine, 2,4,6-collidine, 4-dimethylaminopyridine, quinuclidine, 2,6-di-tert-butylpyridine, tert-butylphosphacene, lithium diisopropylamide, sodium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, lithium tetramethylpiperidide, sodium hydride, potassium hydride, sodium tert-butoxide, and potassium tert-butoxide. In some embodiments, the second non-nucleophilic base is DIPEA. In some embodiments, the second oxidant is selected from O2, N-methylmorpholine oxide (NMO), chloranil (CA), 7,7,8,8-tetracyanoquinodimethane (TCNQ), benzylidene-malononitrile (BMCN), tetracyanoethylene (TCNE), 2,3-dicyano-1,4-benzoquinone (DCBQ), and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). In some embodiments, the oxidant is DDQ. In some embodiments, the process further comprises preparing the compound of formula C or a salt thereof by a process comprising: a) treat the compound of formula 1a Nx ür / X^'O / 1a or a salt thereof with O-(mesethylsulfonyl)hydroxylamine to form the compound of formula 2a b) treat the compound of formula 2a with the compound of formula 27 or A, R4 Or a salt thereof, wherein R4 is a C1-C6 alkyl described herein, to form a mixture of the compounds of formula 3 and formula 4 233789 2665047 of 99 Minutes P 18 01 02928 or you leave it; c) separate the compound of formula 4 from the compound of formula 3; d) treat the compound of formula 4 with a second dilute strong acid to form the compound of formula 5C or a salt of it; e) treating the compound of formula 5C or a salt thereof with a second substituted amide and a second acid chloride to form a compound of formula 6C or a salt of it; f) treat the compound of formula 6C or form a compound of formula 7C or a salt thereof with hydroxylamine to -OH or a salt thereof; and g) treat the compound of formula 7C with a second acid anhydride to form the compound of formula C. In some embodiments, a compound of formula C or a salt thereof can be prepared as shown in Scheme 10, wherein R4 is defined as follows. 233789 2665047 of 99 Minutes P 18 01 02928 Scheme 10 In some embodiments of Scheme 10, R4 is a C1-C6 alkyl group selected from methyl, ethyl, propyl, butyl, pentyl, and hexyl. In some embodiments, the C1-C6 alkyl group is a straight-chain alkyl group. In some embodiments, the C1-C6 alkyl group is branched. In some embodiments, the C1-C6 alkyl group is methyl. In some embodiments, the C1-C6 alkyl group is ethyl. In some embodiments, R4 is ethyl and compound 27 is compound 27a or 27a or salt of the same. In some embodiments, R4 is ethyl and compound 3 is compound 3a or get out of it. In some embodiments, R4 is ethyl and compound 4 is compound 4a or get out of it. 233789 2665047 of 99 Minutes P 18 01 02928 In some embodiments, the compound of formula 4 or a salt thereof is treated with a second dilute strong acid. In some embodiments, the second dilute strong acid is selected from perchloric acid, hydroiodic acid, hydrobromic acid, hydrochloric acid, sulfuric acid, p-toluenesulfonic acid, and methanesulfonic acid. In some embodiments, the second dilute strong acid is dilute hydrobromic acid. In some embodiments, the compound of formula 5C or a salt thereof is treated with a second substituted amide. In some embodiments, the second substituted amide is selected from benzyl methylformamide, N-formylmorpholine, dimethylacetamide, N-methylpyrrolidone, N-methylformanilide, N,N-dimethylformamide (DMF), N-methylformamide, N-formylpiperidine, and N-formylindoline. In some embodiments, the second substituted amide is DMF. In some embodiments, the compound of formula 5C or a salt thereof is treated with a second acid chloride. In some embodiments, the second acid chloride is selected from phosphoryl chloride (POCl3), phosgene (COCl2), thionyl chloride (SOCh), oxalyl chloride (C2O2O2), acetyl chloride (CHsCOCl), an aromatic acid chloride (ArCOCl), an aromatic thionyl chloride (ArSO2Cl), phosphorus pentachloride (PO5), dimethylsulfamoyl chloride (Me2NSO2Cl), and dialkoxysulfamoyl chloride (RO2CNHSO2Q). In some embodiments, the second acid chloride is POCE. In some embodiments, the compound of formula 7C or a salt thereof is treated with a second acid anhydride. In some embodiments, the second acid anhydride is selected from acetic anhydride, formic anhydride, propionic anhydride, butyric anhydride, succinic anhydride, glutaric anhydride, methylsuccinic anhydride, maleic anhydride, methylmaleic anhydride, phthalic anhydride, 1,2,3,6-tetrahydrophthalic anhydride, 3,4,5,6-tetrahydrophthalic anhydride, hexahydrophthalic anhydride, cis-5-norbornene-(endo, exo)-2,3-dicarboxylic anhydride, and mixtures thereof. In some embodiments, the second acid anhydride is acetic anhydride. In some embodiments, a process is provided herein for preparing a pharmaceutical composition comprising mixing (i) a compound of Formula I or a pharmaceutically acceptable salt thereof prepared according to any of the processes described herein, and (ii) a pharmaceutically acceptable carrier. Pharmaceutical compositions containing the compound of Formula I or a pharmaceutically acceptable salt thereof as an active ingredient may be prepared by intimately mixing the compound of Formula I or a pharmaceutically acceptable salt thereof. 233789 2665047 of 99 Acta P 18 01 02928 refers to a pharmaceutical carrier mixed according to conventional pharmaceutical blending techniques. The carrier can take a wide variety of forms depending on the desired route of administration (e.g., oral, parenteral). Thus, for liquid oral preparations such as suspensions, elixirs, and solutions, suitable carriers and additives include water, glycols, oils, alcohols, flavoring agents, preservatives, stabilizers, colorants, and the like; for solid oral preparations such as powders, capsules, and tablets, suitable carriers and additives include starches, sugars, diluents, granulating agents, lubricants, binders, disintegrating agents, and the like. Solid oral preparations may also be coated with substances such as sugars, or they may be enterically coated to modulate the major site of absorption.For parenteral administration, the carrier will usually consist of sterile water, and other ingredients may be added to increase solubility or for preservation. Injectable suspensions or solutions may also be prepared using aqueous carriers along with appropriate additives. The compound of Formula I or a pharmaceutically acceptable salt thereof may be administered by any convenient route, for example, into the gastrointestinal tract (e.g., rectally or orally), the nose, lungs, musculature, or vasculature, or by dermal or transdermal routes. The compound of Formula I or a pharmaceutically acceptable salt thereof may be administered in any convenient dosage form, for example, tablets, powders, capsules, solutions, dispersions, suspensions, syrups, sprays, suppositories, gels, emulsions, patches, etc. Such compositions may contain components that are conventional in pharmaceutical preparations, for example, diluents, carriers, pH modifiers, sweeteners, bulking agents, and other active ingredients. If parenteral administration is desired, the compositions shall be sterile and in a suspension solution suitable for injection or infusion.Such compositions form another aspect of the invention. Pharmaceutical compositions comprising a compound of Formula I or a pharmaceutically acceptable salt thereof are also provided herein. To prepare the pharmaceutical compositions provided herein, the compound of Formula I or a pharmaceutically acceptable salt thereof as the active ingredient is intimately mixed with a pharmaceutical carrier according to conventional pharmaceutical mixing techniques. The carrier may take a wide variety of forms depending on the 233789 2665047 of 99 Acta P 18 01 02928 desired form of preparation for administration, for example, oral or parenteral, such as intramuscular. To prepare the pharmaceutical compositions provided herein, the compound of Formula I or a pharmaceutically acceptable salt thereof as the active ingredient is intimately mixed with a pharmaceutical carrier according to conventional pharmaceutical mixing techniques. The carrier may take a wide variety of forms depending on the desired route of administration (e.g., oral or parenteral). Suitable pharmaceutically acceptable carriers are widely known in the art. Descriptions of some of these pharmaceutically acceptable carriers can be found in The Handbook of Pharmaceutical Excipients, published by the American Pharmaceutical Association and the Pharmaceutical Society of Great Britain. Methods for formulating pharmaceutical compositions have been described in numerous US publications, such as Pharmaceutical Dosage Forms: Tablets, Second Edition, Revised and Expanded, Volumes 1-3, edited by Lieberman et al.; Pharmaceutical Dosage Forms: Parenteral Medications, Volumes 1-2, edited by Avis et al.; and Pharmaceutical Dosage Forms: Disperse Systems, Volumes 1-2, edited by Lieberman et al.; published by Marcel Dekker, Inc. EXAMPLES 1. Preparation of a compound of formula A A. A compound of formula A can be prepared according to the methods described in documents US 2017 / 0096425 and WO 2017 / 011776. Briefly: 1-Amino-3-bromo-5-methoxypyridin-1-ium 2,4,6-trimethylbenzenesulfonate (2a): To a solution of O-(mesethylsulfonyl)hydroxylamine (26.6 g, 117 mmol) in DCM (570 mL) cooled to 0°C, 3-bromo-5-methoxypyridine (22.1 g, 117 mmol) was added in portions. The reaction mixture was stirred for 1 h at 0°C, then treated with additional 3-bromo-5-methoxypyridine (250 mg, 1.39 mmol) and stirred for a further 2 h at 0°C. The reaction mixture was diluted with Et₂O (600 mL), stirred at 0°C for 10 min, then vacuum filtered and rinsed with Et₂O (3 x 250 mL). Given the reduction in volume to approximately 1 / 3, the 233789 75 2665047 of 99 Acta P 18 01 02928 filtrate formed an additional precipitate that was collected by filtration. Both filter cakes were dried in a vacuum to provide the title compound (39.3 g, 83% yield). 1H NMR (CDCh): δ 9.25 (br s, 1H), 8.99 (m, 1H), 8.74 (m, 1H), 7.46 (m, 1H), 6.83 (s, 2H), 3.92 (s, 3H), 2.65 (s, 6H), 2.22 (s, 3H). Ethyl-6-bromo-4-methoxypyrazolo[1,5-a]pyridine-3-carboxylate (3a) and ethyl-4-bromo-6-methoxypyrazolo[1,5-a]pyridine-3-carboxylate (4a): To a magnetically stirred white suspension of 1-amino-3-bromo-5-methoxypyridin-1-iodine 2,4,6-trimethylbenzenesulfonate (2a) (33.24 g, 82.42 mmol) in DMF (82 mL) at room temperature, TEA (22.98 mL, 164.8 mmol) was added, followed by the dropwise addition of ethyl propiolate (16.71 mL, 164.8 mmol). After vigorous stirring for 2 d, the reaction was slowly stopped by partial addition to ice-cold water under rapid stirring (820 mL). The mixture was stirred at room temperature for 10 min and then vacuum filtered. The collected solids were rinsed with water and air dried, forming the title compound as an orange solid in an isomeric ratio of approximately 4:1 (by 1H NMR) with compound 3a as the major isomer (21 g).The wet solid isomeric mixture (approximately 75% w / w) was used directly in the next step without further purification. MS (apci) m / z = 298.9, 300.9 (M+H). The regioisomeric ratio was determined by chemical shift of MeO in 1H NMR (CDCL) δ 3.98 (3a) vs. 3.83 (4a). 6-Bromo-4-methoxypyrazolo[1,5-a]pyridine (5A) and 4-Bromo-6-methoxypyrazolo[1,5-a]pyridine (5C): The isomeric mixture of ethyl-6-bromo-4-methoxypyrazolo[1,5-a]pyridine-3-carboxylate (3a) and ethyl-4-bromo-4-methoxypyrazolo[1,5-a]pyridine-3-carboxylate (4a) described above (15 g, 50.1 mmol) was added to 48% HBr (114 mL) while stirring, then heated at 80 °C for 90 min, followed by stirring at room temperature overnight. The resulting suspension was vacuum filtered and rinsed with water. The aqueous filtrate and filter cake were treated separately. The filter cake was adsorbed onto MTBE. 233789 76 2665047 of 99 Acta P 18 01 02928 and was vacuum filtered to remove insoluble impurities. The filtered MTBE product was dried in the presence of anhydrous Na2SO4, filtered, and concentrated in vacuum to form 6-bromo-4-methoxypyrazolo[1,5-a]pyridine (5A) as a beige solid (approximately 98:2 6- / 4-Br; 5.08 g). MS (apci) m / z = 226.9, 228.9 (M+H). 1H NMR (CDCh): δ 8.26 (m, 1H), 7.82 (d, 1H), 6.61 (m, 1H), 6.43 (m, 1H), 3.94 (s, 3H). Separately, the filtrate from the original aqueous reaction mixture was extracted with EtOAc (2 x 500 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated in vacuo. The crude residue was adsorbed onto DCM (50 mL) and then filtered to remove insoluble solids. Concentration of the DCM filtrate under vacuum followed by silica chromatography (0 to 50% EtOAc / hexanes) yielded a second batch of 6-bromo-4-methoxypyrazolo[1,5-a]pyridine (5A) as a white solid (upper spot Rf, 2.06 g), as well as the minor isomer compound 4-bromo-6-methoxypyrazolo[1,5-a]pyridine (5C), also as a white solid (lower spot Rf, 1.32 g). MS (apci) m / z = 226.9, 228.9 (M+H). 1H NMR (CDCh) δ 8.02 (m, 1H), 7.85 (d, 1H), 7.17 (d, 1H), 6.55 (m, 1H), 3.80 (s, 3H). N=\ O / \ / / Jf TH 6A 6-Bromo-4-methoxypyrazolo[1,5-a]pyridine-3-carbaldehyde (6A): To a 0 °C solution of 6-bromo-4-methoxypyrazolo[1,5-a]pyridine (5A) (0.75 g, 3.303 mmol) in DMF (33 mL), POCl3 (0.92 mL, 9.909 mmol) was slowly added. The reaction was warmed to room temperature and stirred for 4 h, then diluted with H2O (30 mL). The resulting suspension was made basified to pH 9–10 with 1 M NaOH(aq), then stirred for 1 h, vacuum filtered, and then sequentially rinsed with H2O (25 mL) and MTBE (50 mL) to form the title compound (0.76 g, 90% yield). MS (apci) m / z = 256.9 (M+H). (E) -6-bromo-4-methoxypyrazolo[1,5-a]pyridine-3-carbaldehyde oxime (7A): A suspension of 6-bromo-4-methoxypyrazolo[1,5-a]pyridine-3-carbaldehyde (6A) (0.76 g, 3.0 233789 77 2665047 of 99 Acta P 18 01 02928 mmol) and hydroxylamine hydrochloride (0.31 g, 4.5 mmol) in EtOH (40 mL) water (20 mL) was added, and the reaction was stirred at 50 °C for 4 h. After cooling to room temperature, the reaction mixture was concentrated in a vacuum. The residue was resuspended in water, then treated with saturated NaHCO3(aq) and vacuum filtered. The solids were sequentially rinsed with H2O (25 mL) and MTBE (50 mL) to form the title compound (0.68 g, 84% yield). MS (apci) m / z = 271.9 (M+H). 6-Bromo-4-methoxypyrazolo[1,5-a]pyridine-3-carbonitrile (A): A solution of (E)-6-bromo-4-methoxypyrazolo[1,5-a]pyridine-3-carbaldehyde oxime (7A) (17.15 g, 63.50 mmol) in acetic anhydride (707 mL, 7.49 mol) was heated at 120 °C overnight. After subsequent distillation to remove the acetic anhydride, the remaining residue was dried in vacuo to form the title compound (15.92 g, 99.4% yield). 1H NMR (CDCE): δ 8.32 (m, 1H), 8.12 (s, 1H), 6.74 (m, 1H), 4.03 (s, 3H). B. A compound of formula A can also be prepared according to the method described below. 1-Amino-3-bromo-5-methoxypyridin-1-ium 2,4,6-trimethylbenzenesulfonate (2a): To a solution of O-(mesethylsulfonyl)hydroxylamine (146 mol) in DCM (200 kg), 3-bromo-5-methoxypyridine (24.6 kg, 131 mol) was added dropwise at 0–5 °C. The reaction was stirred for 16 h at 0–5 °C. HPLC indicated that the reaction was complete. n-Heptanes (130 kg) were added to the reaction, and the mixture was stirred at 0–5 °C for 1 h. The suspension was filtered, and the filter cake was washed with n-heptane (20 kg x 2) and dried to form compound 2 (40 kg) as a white solid. 1H NMR (400MHz, DMSO-d6), δ (ppm): 8.71 (s, 1H), 8.62 (s, 1H), 8.57 (s, 2H), 8.26 (s, 1H), 6.75 (s, 2H), 3.975 (s, 3H), 2.176 (s, 3H). 233789 2665047 of 99 Minutes P 18 01 02928 TO 6-Bromo-4-methoxypyrazolo[1,5-a]pyridine-3-carbonitrile (A): To a solution of 1-amino-3-bromo-5-methoxypyridin-1-ium 2,4,6-trimethylbenzenesulfonate (2a) (40 kg, 100 mol) in acetonitrile (300 kg), 2-chloroacrylonitrile (13 kg, 150 mol) was added in a portion at -5°C. DBU (56 kg, 370 mol) was added dropwise at -10 to 0°C to the solution. The reaction mixture was stirred at 25–30°C for 16 h. HPLC showed that the reaction was complete. The reaction mixture was stopped with H₂O (900 L), the suspension was filtered, and the solid was washed with H₂O (100 L). The resulting solid was combined with another batch of compound A. DCM (400 L) was added to the combined solids, and the remaining solid was washed with DCM (4 x 400 L). The combined organic layers were concentrated under vacuum. The residue was suspended in n-heptane (80 kg), filtered, and dried to form compound A (20.8 kg, 39.1%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.92 (s, 1H), 8.58 (s, 1H), 7.23 (s, 1H).4,036 (s, 3H). C. A compound of formula A can also be prepared as described below: a. Alternative step-by-step preparation of a compound of formula A: 1-Amino-3-bromo-5-methoxypyridin-1-ium 2,4-dinitrophenolate: To a solution of 3-bromo-5-methoxypyridine (500 mg, 2.66 mmol) in acetonitrile (5 mL), O-(2,4-dinitrophenyl)hydroxylamine (635 mg, 3.19 mmol) is added with stirring at a temperature of 20–25 °C. The mixture is heated to 40 °C. Once the reaction is complete, the heat is turned off, and the mixture is allowed to cool to 20 °C. The solids are filtered, and the cake is washed with MTBE (1 mL). The wet cake is dried under vacuum without heat for 18 h to yield 1-amino-3-bromo-5-methoxypyridin-1-ium 2,4-dinitrophenolate (862 mg, 83.7%). MeCN 4-Bromo-6-methoxypyrazole[1,5-a]pyridine-3-carbonitrile (A): A suspension at 0 at 5 °C of 2,4-dinitrophenolate of N-amino-3-bromo-6-methoxypyridin-1-io (1.60 g, 4.13 mmol) in 233789 2665047 of 99 Acta P 18 01 02928 Acetonitrile (6.4 mL) is added to 2-chloroacrylonitrile (542 mg, 6.20 mmol). 1,8-Diazabicyclo[5,4,0]undec-7-ene (DBU, 2.3 g, 15.29 mmol) is added to the suspension at a rate such that the temperature is maintained below 15 °C. The dark brown solution is maintained at a temperature of 0 to 5 °C for 1.5 h after the addition of DBU. Once the reaction is complete, water (9.6 mL) is added to the mixture and it is stirred for 3.5 h. The mixture is filtered, and the filtrate is used to help transfer all the solids from the flask to the funnel. The solids are washed with hexanes to remove acetonitrile and water from the wet cake. The wet cake is dried under vacuum to provide 4-bromo-6-methoxypyrazolo[1,5-a]pyridine-3-carbonitrile (A) (648 mg, 62.2%). b. Alternative telescopic preparation of a compound of formula A: 4-Bromo-6-methoxypyrazolo[1,5-a]pyridine-3-carbonitrile (A): To a 0 to 5 °C solution of 3-bromo-5-methoxypyridine (6.0 g, 31.91 mmol) in acetonitrile (20 mL), O-(2,4-dinitrophenyl)hydroxylamine (7.6 g, 38.27 mmol) is added with stirring at 20 to 25 °C. An additional charge of acetonitrile (19 mL) is made, and the mixture is heated to 40 °C for 48 h. The heating is turned off, and the mixture is allowed to cool to 0 to 5 °C, and 2-chloroacrylonitrile (1.35 eq based on 3-bromo-5-methoxypyridine, 3.5 mL, 43.20 mmol) is added. 1,8-Diazabicyclo[5,4,0]undec-7-ene (DBU, 3.34 eq based on 3-bromo-5-methoxypyridine, 15.9 mL, 105.56 mmol) is added to the suspension at a rate such that the temperature is maintained below 8 °C. The dark brown solution is kept at 0 to 5 °C for 1.5 h after the DBU addition is complete. Once the reaction is determined to be complete, water (16 mL) is added and the mixture is stirred for 3 h. The mixture is filtered, and 233789 2665047 of 99 Acta P 18 01 02928 The filtrate is used to help transfer all the solid from the flask to the funnel, if necessary. The solids are washed with a water / acetonitrile solution (6.6 mL, 5:1). The wet cake is dried in a vacuum oven at 45 °C for 24 h to provide 4-bromo-6-methoxypyrazolo[1,5-a]pyridine-3-carbonitrile (A) (3.9 g, 49%). 2. Preparation of a compound of formula B 1-Amino-3,5-dibromopyridin-1-ium 2,4,6-trimethylbenzenesulfonate (9): A solution of O-(mesethylsulfonyl)hydroxylamine in DCM (2 L) was added to a solution of 3,5-dibromopyridine (320 g, 1.35 mol) in DCM (2.5 L) at 0-5 °C. The reaction was stirred for 16 h at this temperature before adding ether (5 L) at 0-5 °C. The suspension was then filtered and the cake washed with Et2U (4 L) to form compound 9 (500 g crude). 4,6-Dibromopyrazolo[1,5-a]pyridine-3-carbonitrile (B): To a mixture of compound 9 (40 g, 88.5 mmol) in p-dioxane (400 mL), acrylonitrile (10.72 g, 202 mmol) and DIPEA (14.8 g, 11.5 mmol) were added. The mixture was stirred at room temperature for 3 h, then DDQ (41.8 g, 184 mmol) was added, and the mixture was stirred at room temperature for an additional 3 h. The reaction was monitored by TLC (eluent: ethyl acetate / petroleum ether, 1:2) and showed that compound 9 was consumed. The reaction mixture was poured into water (1.6 L), and the resulting solid was filtered out. The solid was collected and then purified by column chromatography (silica gel column with ethyl acetate / petroleum ether (1:2) elution) to obtain a compound of formula B (13.8 g, 56.5 mmol, 52.1%). 3. Preparation of a compound of formula C A. A compound of formula C can be prepared according to the method described in Provisional Patent Application US No. 62 / 406,252. Briefly: 233789 2665047 of 99 Minutes P 18 01 02928 4-Bromo-6-methoxypyrazolo[1,5-a]pyridine-3-carbaldehyde (6C): A solution of 4-bromo-6-methoxypyrazolo[1,5-a]pyridine (5C) (5.0 g, 22 mmol) in DMF (220 mL) was cooled to 0 °C and then slowly treated with POCE (6.2 mL, 66 mmol). The reaction was warmed to room temperature and stirred overnight. The reaction mixture was cooled to 0 °C, stopped with water (220 mL), and basified with 6 M NaOH(aq) to pH 9–10. The reaction mixture was stirred for 1 h and then vacuum filtered. The solids were sequentially rinsed with water (3 x 50 mL) and MTBE (3 x 50 mL). The collected solid was suspended in DCM (500 mL) and stirred in a sonication bath for 30 min, then vacuum filtered. The filtrate was retained, while the filter cake was absorbed in water (300 mL) and extracted with DCM.The organic extracts, along with the retained DCM filtrate, were combined and dried in the presence of anhydrous Na2SO4, then filtered and concentrated in vacuo to provide the title compound (4.84 g, 86% yield). MS (apci), m / z = 256.9 (M+H). -OH 4-Bromo-6-methoxypyrazolo[1,5-a]pyridine-3-carbaldehyde oxime (7C): To a suspension of 4-bromo-6-methoxypyrazolo[1,5-a]pyridine-3-carbaldehyde (6C) (4.84 g, 19.0 mmol) in EtOH (253 mL) at room temperature, water (127 mL) and hydroxylamine hydrochloride (1.98 g, 28.5 mmol) were added. After stirring at 50 °C overnight, the reaction mixture was cooled to room temperature and concentrated in vacuo. The residue was resuspended in water (150 mL) and then slowly stopped with saturated NaHCO3(aq) (30 mL). After stirring for 1 hour at room temperature, the suspension was vacuum filtered and the filter cake was sequentially rinsed with H2O (500 mL) and MTBE (100 mL) to form the title compound as a 2:1 E / Z mixture (5.13 g, quantitative yield), which was used in the next step without further purification. MS (apci) m / z = 271.9 (M+H). 233789 2665047 of 99 Minutes P 18 01 02928 C 4-Bromo-6-methoxypyrazolo[1,5-a]pyridine-3-carbonitrile (C): The E / Z mixture of 4-bromo-6-methoxypyrazolo[1,5-a]pyridine-3-carbaldehyde oxime (7C) (4.95 g, 18.33 mmol) in acetic anhydride (172.9 mL, 1833 mmol) was stirred at 140 °C for 25 h, and then cooled to room temperature. The resulting suspension was further cooled in an ice bath for 15 min and then vacuum filtered and sequentially rinsed with water (200 mL) and MTBE (300 mL) to provide the title compound (3.74 g, 81% yield). 1H NMR (Ó6-DMSO): δ 8.70 (s, 1H), 8.60 (s, 1H), 7.78 (s, 1H), 3.83 (s, 3H). 4. Preparation of the compound of Formula IA. Starting from a compound of formula A 6-Bromo-4-hydroxypyrazolo[1,5-a]pyridine-3-carbonitrile (18): A solution of 6-bromo-4-methoxypyrazolo[1,5-a]pyridine-3-carbonitrile (A) (20.8 kg, 82.5 mol) in DMF (200 kg) was added in one portion at 40 °C. 1-Dodecanethiol (33.5 kg, 165 mol) was added to the solution at 40–45 °C, and the reaction mixture was stirred at 50 °C for 16 h. HPLC showed that the reaction was complete. The reaction mixture was poured into water (900 kg) at 0–5 °C, followed by 10% aqueous citric acid monohydrate, which was used to adjust the pH to 5–6. The mixture was extracted with ethyl acetate (400 L x 3). The combined organic layers were washed with brine and concentrated under reduced pressure. The residue was suspended in n-heptane (80 kg) and filtered, and the filter cake was washed with n-heptane (20 kg x 2) and dried to form 18 (17.8 kg, 90.8%) as a yellow solid. 1H NMR (400MHz, DMSO-d6) δ (ppm): 8.75 (s, 1H), 8.51 (s, 1H), 6.84 (d, 1H). 233789 2665047 of 99 Minutes P 18 01 02928 6-Bromo-3-cyanopyrazolo[1,5-a]pyridin-4-yl trifluoromethanesulfonate (19): To a solution of 6-bromo-4-hydroxypyrazolo[1,5-a]pyridine-3-carbonitrile (18) (17.8 kg, 74.8 mol) in DMF (170 kg), DIPEA (19.0 kg, 147 mol) was added in portions at -5 to 5 °C. N,Nbis(trifluoromethylsulfonyl)aniline (26.2 kg, 73.5 mol) was added in portions to the previous solution at -5 to 0 °C. The reaction mixture was stirred at 0 °C for 1 h. TLC (petrol ether:ethyl acetate, 2:1, Rf=0.5) showed that the reaction was complete. The reaction was stopped by the addition of H2O (500 kg), and a suspension was formed. The solid was obtained by filtration and then dissolved in ethyl acetate (300 L) and brine (70 L). The organic layer was concentrated to 30 L and n-heptane (80 kg) was added. The suspension was stirred at 30 °C for 0.5 h, then filtered. The solid was washed with n-heptane (20 kg x 2), dried to form 19 (22.5 kg, 81.0%) as a white solid. 1H NMR (400 MHz, CDCh) δ (ppm): 8.768 (s, 1H), 8.321 (s, 1H), 7.60 (s, 1H), 3.84 (s, 3H). 6-bromo-4-(6-fluoropyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile (20a): To a solution of 6-bromo-3-cyanopyrazolo[1,5-a]pyridin-4-yl trifluoromethanesulfonate (19) (21.5 kg, 58 mol), 2-fluoro-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (12) (12.9 kg, 58 mol) and Pd(dppf)Cl2.DCM (1.4 kg, 1.7 mol) in THF (400 kg) under an atmosphere of N2, an aqueous solution of potassium acetate (11.5 kg in 100 kg of water) was added at 10 °C. The reaction mixture was stirred at 25-30 °C for 48 h. HPLC showed that the reaction was complete. The reaction was stopped by the addition of water (150 kg) and the suspension was filtered. The solid was suspended in MeOH (200 L) and the suspension was stirred at 25–30 °C for 0.5 h and filtered. The filter cake was washed with MeOH (50 L) and dried to form the crude product (17 kg), which was purified by recrystallization to form 20a (15.03 kg, 81.6%) as a white solid. The recrystallization process was as follows: DMF (36 kg) was added to a solution of crude product 20a (17 kg) in THF (600 L) at 60°C. The mixture was stirred at 60°C for 0.5 h. The mixture was cooled to 20°C and water (300 L) was added, followed by filtration. The filter cake was washed with water (100 L) and dried to form compound 20 (15.0 kg, 82%). 1H NMR (DMSO-d6, 40 MHz) δ (ppm): 9.48 (s, 1H), 8.73 (s, 1H), 8.51 (s, 1H), 8.25-8.29 (m, 1H), 7.86 (d, 1H), 7.38-7.41 (m, 1H). HPLC: 99.33%. MS: [M] = 316.8, [M+2] = 318.8. 233789 84 2665047 of 99 Minutes P 18 01 02928 13a 4-(6-fluoropyridin-3-yl)-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3carbonitrile (13a) Direct synthesis: A reaction vessel was charged with 6-bromo-4-(6-fluoropyridin-3-yl)pyrazolo[1,5a]pyridine-3-carbonitrile (20a) (7.8 kg, 5.68 mol), p-dioxane (28 L), water (9.5 L), and CS2CO3 (5.55 kg, 17.03 mol). The mixture was stirred and purged with N2 for at least 30 min. The flask was then charged with di-tert-butyl(2',4',6'-triisopropyl-3,4,5,6-tetramethyl-[1,1'-biphenyl]-2-yl)phosphane (436 g, 908 mmol), Pd2(dba)3 (208 g, 227 mmol), and p-dioxane (0.8 L). The mixture was stirred and purged with N2 for at least 30 min, then charged with 2,2-dimethyloxirane (5.04 L, 56.8 mol), and the reaction was heated to 72 °C overnight and into the following day. Samples of the reaction were taken to confirm completion. Heating was stopped, and the reaction was allowed to cool. When the internal temperature reached approximately 40 °C, Darco G60 (180 g) was added. The reaction was stirred (while continuing to cool) for at least 1 h. When the reaction mixture reached approximately 30 °C, it was filtered in the presence of Celite (2.7 kg).The Celite cake was rinsed with ethyl acetate (7.2 L x 5). The mixture was diluted with water (18 L) and the phases separated. The organic layer was washed with a 1:1 water / brine solution (36 L). The layers were separated. The aqueous layers were combined and extracted with ethyl acetate (18 L). The layers were separated, and the organic layers were concentrated to 18 L (bath temperature 35 °C). Silicicle (2.3 kg) and activated carbon (1.8 kg) were loaded onto the organic layer. The mixture was heated to 50 °C and stirred overnight. The reaction was cooled to room temperature and then filtered in the presence of Celite (2.2 kg). The Celite cake was rinsed with ethyl acetate (10.8 L and then 14.4 L). The solvent was extracted under vacuum until a total of approximately 3.6 L was obtained. A charge of MTBE (3.6 L) was added, and the solvent was concentrated to 3.6 L. This step was repeated twice more, and the mixture was stirred at room temperature overnight. The mixture was filtered, and the filter cake was rinsed with MTBE (3.6 L x 2).The solids were transferred to a vacuum oven and dried to form 13 (1085 g, 89% by weight, 56% corrected yield). 233789 85 2665047 of 99 Minutes P 18 01 02928 Step-by-step summary: 4-(6-fluoropyridin-3-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolo[1,5a]pyridine-3-carbonitrile (22a): A reaction flask loaded with 6-bromo-4-(6fluoropyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile (20a) (50.2 g, 153 mmol), bis(pinacolato)diboron (40.9 g, 161 mmol), and potassium acetate (45.2 g, 460 mmol) were suspended in DMSO (395 mL, 0.4 M) and then sparged with argon for 10 min. The reaction mixture was then treated with Pd(dppf)Cl₂'DCM (1.25 g, 1.54 mmol) and sprayed with argon for an additional 10 minutes. The reaction mixture was heated to 70 °C for 16 h under a backflow of N₂ and then cooled to room temperature. The mixture was then diluted with ethyl acetate (2 L) and water (2 L). The two-phase mixture was stirred for 1 h, then the solids were removed by filtration, and the cake was washed with ethyl acetate (250 mL). The layers were separated, and the aqueous layer was extracted with ethyl acetate (1 L).The combined organic layers were washed with water (1 L x 2) and then brine (1 x 250 mL). The organic layer was dried with Na₂SO₄ and filtered. The filtrate was treated with 15 g of Si-thiol resin and stirred for 16 h. Solids were removed by filtration, and the cake was washed with ethyl acetate. The organic layers were concentrated under vacuum to form Compound 22a (54.1 g, 85.8 wt%). Compound 22a was used directly in the next step. 4-(6-fluoropyridin-3-yl)-6-hydroxypyrazolo[1,5-a]pyridine-3-carbonitrile (23a): 4-(6-fluoropyridin-3-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile (22a) (54.1 g, 127.5 mmol) was dissolved in THF (750 mL, 0.2 M) and cooled to ~3 °C under a backflush of N2. The reaction mixture was then treated with sodium hydroxide (319 mL, 637 mmol) and allowed to cool again to ~3 °C. The mixture was treated dropwise with cooled (~2°C) 35% hydrogen peroxide (89 mL, 1.02 mol) at a rate of ~1 drop every 233789 86 2665047 of 99 Acta P 18 01 02928 seconds. The mixture was stirred for 4 h after the complete addition of peroxide. To ensure the reaction was completed, an additional 1.0 equiv. of H2O2 was added, and the mixture was stirred at ~3 °C for an additional 1 h. The reaction mixture was then treated dropwise at a rate of ~2 drops per second with sodium thiosulfate (382 mL, 1.1 mol) at 3 °C and then allowed to warm slowly to room temperature and stirred for 16 h. The mixture was diluted with MTBE (1.5 L) and water (500 mL) and stirred at room temperature for 30 minutes. The layers were separated, and the organic layer was washed with 0.1 M NaOH (200 mL). The combined aqueous layers were extracted with MTBE (500 mL). The aqueous layer was acidified to pH ~5 using solid citric acid and then diluted with water (1 L) and allowed to be stirred for 1 h. The solids were filtered, rinsed with additional water (~200 mL), and dried under vacuum for ~60 h to form 23a (25.6 g, 81%). 13a 4-(6-fluoropyridin-3-yl)-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-carbonitrile (13a): 4-(6-fluoropyridin-3-yl)-6-hydroxypyrazolo[1,5-a]pyridine-3-carbonitrile (23a) (2.46 g, 9.68 mmol) was dissolved in DMF (48 mL, 0.2 M) and cooled to 0 °C. The mixture was then treated with sodium hydroxide (4.98 mL, 9.97 mmol) and stirred at 0 °C for 15 minutes and then treated with isobutylene oxide (8.50 mL, 96.8 mmol), sealed, and heated to 80 °C for 48 h. The mixture was cooled to room temperature, diluted with water (500 mL), and acidified to pH ~5 using solid citric acid and stirred for 30 minutes. The mixture was extracted with ethyl acetate (500 mL x 2). The combined organic layers were washed with water (250 mL x 2) and brine (100 mL), dried in the presence of Na₂SO₄, filtered, and concentrated. The concentrated product was purified by silica gel chromatography (1 to 50% DCM / acetone) to form 13a (1.94 g, 61%). 15a 233789 87 2665047 of 99 Minutes P 18 01 02928 Tert-butyl-3-(5-(3-cyano-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridin-4-yl)pyridin2-yl)-3,6-diazabicyclo[3,1,1]heptane-6-carboxylate (15a): One reactor was charged with 4-(6fluoropyridin-3-yl)-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-carbonitrile (13a) (50 g, 153 mmol), tert-butyl 3,6-diazabicyclo[3,1,1]heptane-6-carboxylate (14a) (42.5 g, 215 mmol), DMSO (200 mL), and KOAc (30.1 g, 306 mmol). The reaction was heated to 75 °C with stirring for 24 h. The batch was cooled to ~15 °C, and water (50 mL) was added at a rate to maintain the internal temperature <35 °C. The mixture was stirred for 30 min. The suspension was filtered, and the cake was washed with 30% DMSO / water (200 mL) and then with water (200 mL). Acetone (200 mL) was added to the cake, and after 2 h, the solid was transferred to a vacuum oven and dried at 45 °C to form 15a (66.2 g, 87%). 4-(6-(3,6-diazabicyclo[3,1,1]heptan-3-yl)pyridin-3-yl)-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-carbonitrile (16): A reactor was charged with tert-butyl 3-(5-(3-cyano-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridin-4-yl)pyridin-2-yl)-3,6-diazabicyclo[3,1,1]heptane-6-carboxylate (15a) (80 g, 159 mmol) and 5% IPA / water (320 mL). The reaction was heated to 45 °C. H2SO4 (35 mL, 634 mol) was charged to the reaction at a rate to maintain the internal temperature below 60 °C. The reaction mixture was allowed to stand at 45 °C for 2 h and then cooled to <30 °C. Isopropyl alcohol (IPA, 720 mL) was added slowly over 5 minutes, and the reaction was stirred for at least 1 h. The slurry was filtered, and the cake was rinsed with IPA (160 mL), then 1:1 IPA / MTBE (160 mL), and then MTBE (160 mL x 2). The cake was dried in a vacuum oven at 45 °C to form a whitish solid (70.4 g, 92 wt%, 74% adjusted yield). Yo 233789 2665047 of 99 Minutes P 18 01 02928 6-(2-hydroxy-2-methylpropoxy)-4-(6-(6-((6-methoxypyridin-3-yl)methyl)-3,6diazabicyclo[3,1,1]heptan-3-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile (I): A reactor was charged and TEA (12.2 mL, 87.4 mmol). Sodium triacetoxyborohydride (STAB) (10.6 g, 50.0 mmol) was added to the reaction mixture in two parts. The reaction was stirred overnight at room temperature. An additional portion of STAB (2.65 g, 12.5 mmol) was added. The reaction was stirred for an additional 2 h at room temperature and its completion was determined by HPLC analysis. The reaction mixture was diluted with water (150 mL) and DCM (225 mL), and the layers were separated. The organic layer was washed with 1:1 water / sat. NaHCO3 (2 x 150 mL) and 1:1 water / brine (150 mL).The organic layer was concentrated under vacuum to approximately 300 mL and then heated to approximately 32°C to produce a homogeneous solution. Heptane (105 mL) was added slowly, and the suspension was allowed to cool to 25°C. An additional heptane charge (195 mL) was added, and the suspension was stirred at room temperature for 3 h. The solids were collected by filtration, and the filter cake was rinsed with heptane (30 mL x 2) and MTBE (30 mL x 2). The cake was dried in a vacuum oven at 45°C to form the compound of Formula I as a whitish solid (10.5 g). The compound of Formula I was recrystallized as follows. A reaction flask was charged with I₂ (10.1 g) and DMSO (110 mL). The mixture was heated to 50 °C until all the solid was in solution. The mixture was cooled to 25 °C and polished filtered. DMSO (10 mL) was added through the filter as a wash. The resulting solution was heated to 45 °C and water (5 mL) was added slowly. The mixture was stirred for 30 minutes and a seed bed was formed. Water (25 mL) was added 1 h and the suspension was allowed to stand at 45 °C for an additional 1 h. The suspension was then allowed to cool to 25 °C and stirred for 2 h. The suspension was filtered and the cake was washed with water (20 mL x 3), MeOH (20 mL x 2), and MTBE (20 mL x 2). The cake was dried at room temperature in a vacuum oven to form 9.35 g (74%) of the compound of Formula I. MS (apci) m / z = 526.2 (M+H).1H NMR (400 MHz, DMSO-d5) δ: 8.64 (d, 1H, J=2.3 Hz), 8.55 (s, 1H), 8.38 (d, 1H, J=2.3 Hz), 8.04 (d, 1H, J=2.8 Hz), 7.64 (d, 1H, J=2.8 Hz), 2.3 Hz), 7.64 (dd, 1H, J=8.6, 2.3 Hz), 7.27 (d, 1H, J=2.0 Hz), 6.76 (d, 1H, J=8.6 Hz), 6.73 (d, 1H, J=8.2 Hz), 4.67 (s, 1H, J=8.2 Hz), s 3.79 (s, 3H), 3.72 (d, 2H, J=12.5 Hz), 3.64 (d, 2H, J=5.9Hz), 3.51 (br d, 2H), 3.47 (s, 2H), 2.47 (m, 1H), 233789 2665047 of 99 Acta P 18 01 02928 B. From a compound of formula A 4-methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole[1,5-a]pyridine-3carbonitrile (32a): To a reaction vessel was loaded 6-bromo-4-methoxypyrazole[1,5a-a-carbonitrile-2003] g, 793.4 mmol), KOAc (233.6 g, 2.38 mol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (261.9 g, 1.03 mol), and p-dioxane (3000 mL). The reaction was degassed for 20 minutes at room temperature. Pd(dppf)DCM (12.96 g, 15.87 mmol) was loaded into the reaction. The reaction was degassed for 20 minutes at room temperature and then heated to 75 °C overnight. The reaction was cooled to room temperature, activated carbon (20 g) was loaded, and the suspension was stirred at room temperature for > 2 hours. The mixture was filtered in the presence of Celite (200 g), and the cake was rinsed with EtOAc (7 x 400 mL). The mixture was added to a reactor and then washed with water (2000 mL). The aqueous layer was extracted, and the organic layer was washed with 3:1 water / brine (2000 mL) and then 1:1 water / brine (2000 mL). The first aqueous layer was extracted again with EtOAc (1000 mL). The combined organic layers were added to a flask, and siliciclethiol (240 g) and activated carbon (100 g) were added.The suspension was heated to 50°C and stirred overnight. The reaction was cooled to below 30°C and filtered in the presence of Celite (250 g). The filter cake was rinsed with EtOAc (6 x 400 mL). The filtrate was distilled under vacuum with heating to a fixed volume, and a thick suspension was formed. Heptane was added slowly over approximately 10 minutes (400 mL) to the suspension, and the mixture was distilled again to a fixed volume. An additional charge of heptane (400 mL) was made, and distillation continued until a fixed volume was reached. The vacuum was released, and heating was stopped. Heptane (200 mL) and MTBE (50 mL) were added, and the suspension was stirred overnight. After overnight stirring, it was apparent that solvent was lost, and heptane (1250 mL) was added slowly. The suspension was left to stand at room temperature for ~10 minutes and then filtered.The cake was rinsed with heptane (2 x 200 mL) and dried at room temperature by passing it through air to form 32a (168.2 g, 87% by weight, 62% corrected yield). 233789 90 2665047 of 99 Minutes P 18 01 02928 6-Hydroxy-4-methoxypyrazolo[1,5-a]pyridine-3-carbonitrile (33): A flask was charged with 4-methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile (32a) (100.0 g, 334.3 mmol), NMO (78.3 g, 668.6 mmol, 2 eq), and THF (1000 mL, 10 vol). The reaction was heated to 50 °C for 1 hour and then additional NMO (19.5 g, 167 mmol, 0.5 eq) was charged. After 1 hour, an additional charge of NMO (19.5 g, 167 mmol, 0.5 eq) was added, and the reaction was heated at 45 °C overnight. After stirring overnight, the reaction was heated again to 50 °C, and NMO (40 g, 334 mmol, 1 eq) was added. After heating for 5 hours, the reaction was distilled to a total volume of 600 mL (the internal temperature was maintained between 42 °C and 50 °C during distillation). The mixture was cooled to 40 °C, and water was added (1800 mL total, 18 vol). A suspension was produced, and an additional 500 mL of water was added.The thick suspension was allowed to stand at room temperature overnight and then filtered. The cake was washed with water (250 mL) and heptane (250 mL) and the solid was dried under vacuum at 50 °C overnight to form 33 (49.6 g, 95.3 wt.%, 85.9% corrected yield based on 87 wt.% 32a). 6-(2-Hydroxy-2-methylpropoxy)-4-methoxypyrazolo[1,5-a]pyridine-3-carbonitrile (34): A flask was loaded with 6-hydroxy-4-methoxypyrazolo[1,5-a]pyridine-3-carbonitrile (33) (10.00 g, 52.86 mmol) and THF (50.0 mL, 5 vol). NaOH (28 mL, 2M) was added in a portion, and after stirring for approximately 5 minutes, 2,2-dimethyloxirane (23.5 mL, 264.3 mmol) was added. The reaction was heated to 60 °C and then stirred overnight. The reaction was cooled to room temperature, THF (10.0 mL) was added, and then water (200 mL) was added slowly. A suspension was produced, and an additional 25 mL of water was added. The solid was filtered, the cake was washed with water (3 x 20 mL), heptane (20 mL), and dried under vacuum at 50 °C to form 34 (10,273 g, 96.2% by weight, 75.1% corrected yield based on 95% by weight 33). 233789 91 2665047 of 99 Minutes P 18 01 02928 N=\ Nkzz~~CN 4-Hydroxy-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-carbonitrile (35): A flask was charged with 6-(2-hydroxy-2-methylpropoxy)-4-methoxypyrazolo[1,5-a]pyridine-3-carbonitrile (34) (8.00 g, 30.62 mmol) and DMA (40 mL, 5 vol). NaOH (2.40 mL, 50 wt%) was added and the mixture was heated to 30 °C. Dodecane-1-thiol (11.1 mL, 45.93 mmol) was added and the mixture was heated to 60 °C. The reaction was determined to be complete and heating was stopped. Water (24 mL, 3 vol) was added to the reaction (~60 °C) and the mixture was allowed to cool to room temperature. The reaction mixture was slowly added (temperature <20°C during addition) to 15 wt% citric acid (160 mL), precooled to 10 °C. The solids were filtered, the cake was washed with water (2 x 16 mL), heptane (3 x 16 mL) and dried under vacuum at 50 °C overnight to form 35 (6,333 g, 93 wt%, 81% corrected yield based on 96 wt% 34). N=\ HO. O OTf 3-Cyano-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-4-yl trifluoromethanesulfonate (36): A flask was loaded with 4-hydroxy-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-carbonitrile (35) (3.31 g), 1,1,1-trifluoro-N-phenyl-N-((trifluoromethyl)sulfonyl)methanesulfonamide (4.79 g), and DMA (33 mL, 10 vol). DIEA (4.67 mL) was added, and after 10 minutes, the reaction was determined to be complete. The reaction mixture was added slowly (maintaining the temperature <20°C) to HOAc (0.92 mL, 1.2 eq) in water (33 mL) that had been pre-cooled to 15°C (ice-water bath). The suspension was stirred for 15 minutes and the solids were filtered out, the cake was washed with water (3 x 7 mL), heptane (2 x 7 mL), and then dried under vacuum at 50 °C to form 36 (3,517 g, 99.4% by weight, 68.9% yield (uncorrected)). 233789 2665047 of 99 Minutes P 18 01 02928 4-(6-fluoropyridin-3-yl)-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-carbonitrile (13): A flask was loaded with 3-cyano-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5a]pyridin-4-yl trifluoromethanesulfonate (36) (3.00 g, 7.91 mmol), 2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (1.85 g, 8.30 mmol), and THF (60 mL, 20 vol). The solution was purged with nitrogen for 15 minutes, and PdCl2(dppf)DCM (452 ​​mg, 0.553 mmol) was added, and the mixture was purged with nitrogen for an additional 5 minutes. KOAc (1.55 g, 15.82 mmol) and water (15 mL) were added to a separate flask. This mixture was purged with nitrogen for 2 minutes and then added to the reaction mixture, which was purged with nitrogen for an additional 5 minutes. The reaction was stirred overnight at room temperature. The reaction mixture was poured over MTBE (60 mL) and water (45 mL). The layers were separated, and the organic layer was washed with water (30 mL) followed by a 3:1 water / brine solution (30 mL).The first and second aqueous layers were combined and extracted again with MTBE (30 mL). The organic layers were combined and concentrated into a solid. The solid was adsorbed onto MTBE (30 mL), and after stirring for 2 hours at room temperature, the suspension was filtered, the cake was washed with heptane (3 x 6 mL), and the solids were dried under vacuum to form Compound 13 (1.69 g, 65% yield). Compound 13 was converted to the compound of Formula I as described above. C. Starting from a compound of formula B 25a Tert-butyl 3-(5-(6-bromo-3-cyanopyrazolo[1,5-a]pyridin-4-yl)pyridin-2-yl)-3,6diazabicyclo[3,1,1]heptane-6-carboxylate (25a): A solution of 4,6dibromopyrazolo[1,5-a]pyridine-3-carbonitrile (B) (0.295 g, 0.980 mmol) and tert-butyl 3-(5 233789 2665047 of 99 Acta P 18 01 02928 (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)-3,6-diazabicyclo[3,1,1]heptane-6-carboxylate (24a) (0.413 g, 1.03 mmol) in DMF (9.8 mL, 0.980 mmol) was heated to 50 °C to solubilize all solids. The mixture was then cooled to room temperature. Aqueous K2CO3 (0.980 mL, 1.96 mmol) was slowly added and the mixture was purged with Ar gas for 5 min. Pd(dppf)Cl2.CH2Cl2 (60 mg, 0.0735 mmol) was then added and the reaction was stirred at room temperature for 48 h. LCMS indicated that the reaction was complete. Ethyl acetate and water were added to the mixture. The layers were separated, and the organic layer was washed with water and brine and dried with Na2SO4. The organic layer was concentrated under vacuum and then purified using column chromatography (hexanes / ethyl acetate, 10-90%) to form 25a (0.332 g, 0.670 mmol, 68.4% yield). 26a Tert-butyl 3-(5-(3-cyano-6-hydroxypyrazolo[1,5-a]pyridin-4-yl)pyridin-2-yl)-3,6diazabicyclo[3,1,1]heptane-6-carboxylate (26a): Tert-butyl 3-(5-(6-bromo-3cyanopyrazolo[1,5-a]pyridin-4-yl)pyridin-2-yl)-3,6-diazabicyclo[3,1,1]heptane-6-carboxylate (25a) (475 mg, 0.959 mmol) was dissolved in THF (10 mL, 0.1 M) and treated with bis(pinacolato)diboron (255 mg, 1.00 mmol), dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium (II).dichloromethane (39 mg, 0.0479 mmol), and potassium acetate (282 mg, 2.88 mmol). The reaction mixture was argon-sprayed, sealed, and heated to 70 °C for 16 h. The reaction was determined to be complete, and the mixture was then cooled to 0 °C and treated with sodium hydroxide (4.8 mL, 4.79 mmol), followed by partial treatment with hydrogen peroxide (0.49 mL x 15, 7.35 mL) every 15 minutes. After complete addition of hydrogen peroxide, the reaction mixture was allowed to warm slowly to room temperature and stirred for 16 h.The reaction mixture was diluted with water and extracted with 4:1 DCM:IPA (2x). The aqueous layer was acidified to pH ~5 using AcOH and extracted with 4:1 DCM:IPA (2x). The combined organic layers were washed with water, dried in the presence of Na2SO4, filtered, and concentrated. The concentrated product was purified by silica gel chromatography (5 to 75% DCM / acetone) to form 26a (314 mg, 75.7%). 233789 94 2665047 of 99 Minutes P 18 01 02928 15a Tert-butyl 3-(5-(3-cyano-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridin-4-yl)pyridin2-yl)-3,6-diazabicyclo[3,1,1]heptane-6-carboxylate (15a): Tert-butyl 3-(5-(3-cyano-6-hydroxypyrazolo[1,5-a]pyridin-4-yl)pyridin-2-yl)-3,6-diazabicyclo[3,1,1]heptane-6-carboxylate (26a) (312 mg, 0.721 mmol) was dissolved in DMF (4.8 mL, 0.15 M) and treated with sodium hydroxide (794 μL, 0.794 mmol). The reaction mixture was stirred for 10 minutes, then treated with isobutylene oxide (634 μL, 7.21 mmol), sealed, and heated at 80 °C for 16 h. The reaction mixture was cooled to room temperature, diluted with water (100 mL), and stirred for 30 minutes. The solid was filtered and rinsed with water to yield 15a (304 mg, 84%) as a light bronze-colored solid. Compound 15a was converted to the compound of Formula I as described above (from a compound of formula A). D. Starting from a compound of formula C The compound of Formula I can also be prepared according to the method described in Provisional Patent Application US No. 62 / 406,252. Briefly: 4-Bromo-6-hydroxypyrazolo[1,5-a]pyridine-3-carbonitrile (10): A suspension of 4-bromo-6-methoxypyrazolo[1,5-a]pyridine-3-carbonitrile (C) (50.0 g, 198.4 mmol) in DCE (500 mL) was treated with AlCl3 (79.34 g, 595.1 mmol). Under an N2(g) atmosphere, the resulting mixture was stirred for 19 h at 76 °C before cooling to room temperature. Using THF (1750 mL) as the rinsing solvent, the reaction mixture was poured into a mechanically stirred suspension of sodium sulfate decahydrate (10 eq, 639 g) in THF (1000 mL). After stirring overnight at room temperature, the resulting suspension was filtered, and the solids were rinsed with additional THF (2 x 250 mL). The filtered product was concentrated in a vacuum, and the resulting solid was dried under high vacuum for 3 days. 233789 2665047 of 99 Acta P 18 01 02928 obtain the title compound (46.18 g, 98% yield) in sufficient purity for further use. 1H NMR (d-DMSO): δ 10.48 (s, 1H), 8.58 (s, 1H), 8.38 (d, 1H), 7.64 (3, 1H). 4-Bromo-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-carbonitrile (11): In a pressure vessel, a mixture of 4-bromo-6-hydroxypyrazolo[1,5-a]pyridine-3-carbonitrile (10) (10.0 g, 42.0 mmol) and K2CO3(s) (17.4 g, 126 mmol) in DMF (50 mL) was treated with 2,2-dimethyloxirane (36.9 mL, 420 mmol). After sealing the vessel, the reaction mixture was stirred for 12 h at 60 °C, then for 12 h at 85 °C. The mixture was allowed to cool to room temperature. The room-temperature mixture was poured into water (400 mL), then stirred for 1 hour at room temperature. The resulting suspension was vacuum filtered and the filter cake was rinsed with water. The solids were collected and vacuum dried to provide the title compound in clean form (11 g, 84% yield). 13a 4-(6-fluoropyridin-3-yl)-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3carbonitrile (13a): A mixture of 4-bromo-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5a]pyridine-3-carbonitrile (11) (10.0 g, 32.2 mmol), 2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2dioxaborolan-2-yl)pyridine (10.8 g, 48.4 mmol) and Pd(PPh3)4 (1.12 g, 0.967 mmol) in dioxane (200 mL) were treated with 2 M Na2CO3(aq) (64.5 mL, 129 mmol). The resulting mixture was sprayed with Ar(g), then stirred for 12 h at 85 °C under an atmosphere of N2(g). After cooling to room temperature, the resulting mixture was poured into cold water (1.5 L). The pH of the mixture was adjusted to approximately pH 6 by adding 10% citric acid. After stirring for 1 h at room temperature, the resulting suspension was vacuum filtered. The solids were collected and vacuum dried to provide a clean compound of the title (10 g, 95% yield). 233789 2665047 of 99 Minutes P 18 01 02928 15a Tert-butyl 3-(5-(3-cyano-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridin-4-yl)pyridin2-yl)-3,6-diazabicyclo[3,1,1]heptane-6-carboxylate (15a): A mixture of and K2CO3(s) (7.88 g, 57.0 mmol) in DMSO (7 mL) was stirred for 12 h at 90 °C. The resulting thick suspension was diluted with an additional DMSO (2 mL) and stirred for 12 h at 90 °C. The mixture was cooled to room temperature and diluted with water (100 mL). The aqueous mixture was washed with DCM. The combined organic extracts were dried in the presence of anhydrous MgSO4(s), filtered, and concentrated in vacuo. The crude residue was purified by silica chromatography (30–80% EtOAc / hexanes as the gradient eluent system) to provide the title compound in clean form (2.87 g, 100% yield). MS (apci) m / z = 505.2 (M+H). 4-(6-(3,6-diazabicyclo[3,1,1]heptan-3-yl)pyridin-3-yl)-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-carbonitrile dihydrochloride (16): A solution of tert-butyl 3-(5-(3-cyano-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridin-4-yl)pyridin-2-yl)3,6-diazabicyclo[3,1,1]heptane-6-carboxylate (15a) (3.05 g, 6.04 mmol) in DCM (20 mL) was treated with 4 N HCl in dioxanes (15.1 mL, 60.4 mmol). The resulting mixture was stirred for 12 h at room temperature, and then concentrated in vacuo. The crude residue was diluted with DCM and toluene, then sonicated before in vacuo concentration to obtain the title compound as the hydrochloride salt (2.44 g, quantitative yield). MS (apci) m / z = 405.2 (M+H). 233789 2665047 of 99 Minutes P 18 01 02928 Yo 6-(2-hydroxy-2-methylpropoxy)-4-(6-(6-((6-methoxypyridin-3-yl)methyl)-3,6 diazabicyclo[3,1,1]heptan-3-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrilo (I): A solution of 4-(6-(3,6-diazabicyclo[3,1,1]heptan-3-yl)pyridin-3-yl)-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-carbonitrile dihydrochloride (16) (12.2 mg, 0.0277 mmol) in DCE (513 pL) was sequentially treated with 6-methoxynicotinaldehyde (7.59 mg, 0.0553 mmol) and NaBH(AcO)3 (17.6 mg, 0.0830 mmol), then stirred overnight at room temperature. The mixture was concentrated in vacuo, and the residue was purified by silica chromatography (0-20% MeOH in DCM as gradient eluent) to provide the title compound in clean form (13.59 mg, 93% yield). MS (apci) m / z = 526.2 (M+H). 1H NMR (400 MHz, DMSO- d5) δ: 8.64 (d, 1H, J=2.3 Hz), 8.55 (s, 1H), 8.38 (d, 1H, J=2.3 Hz), 8.04 (d, 1H, J=2.3 Hz), 7.80 (dd, 1H, J=8.6, 2.3 Hz), 7.64 (dd, 1H, J=8.6, 2.3 Hz), 7.27 (d, 1H, J=2.0 Hz), 6.76 (d, 1H, J=8.6 Hz), 6.73 (d, 1H, J=8.2 Hz), 4.67 (s, 1H), 3.85 (s, 2H), 3.79 (s, 3H), 3.72 (d, 2H, J=12.5 Hz), 3.64 (d, 2H, J=5.9Hz), 3.51 (br d, 2H), 3.47 (s, 2H), 2.47 (m, 1H), 1.55 (d, 1H), 1.20 (s, 6H). 233789 2665047 of 99 20225952036 CRISTIAN DANIEL BITTEL - 20225952036 Digitally signed by PORTALTRAMITES - INPI Date: 2024.03.18 15:50:13 -03:00 Reason: Digitally Signed by the INPI Location: Buenos Aires, Argentina 2665047

Claims

1. A process for preparing a compound of Formula I, FOLLOWS FORMULA 1, or a pharmaceutically acceptable salt thereof, said process being characterized in that it comprises: a) treating a compound of formula 35, FOLLOWS FORMULA 2, or a salt thereof with a first triflation reagent to form a compound of formula 36, ​​FOLLOWS FORMULA 3, or a salt thereof; b) treating the compound of formula 36 or a salt thereof with a compound of formula 12, FOLLOWS FORMULA 4, or a salt thereof, wherein X represents a halogen or a sulfonate and R6 represents an ester or boronic acid with the boron atom as the attachment point to the pyridine ring of compound 12, in the presence of a third catalyst comprising a metal to form the compound of formula 13 or a salt thereof;FOLLOWS FORMULA 5, c) treating a compound of formula 13 or a salt thereof, wherein X represents a halogen or a sulfonate, with a compound of formula 14, FOLLOWS FORMULA 6, or a salt thereof, wherein R1 is an amine protecting group, to form the compound of formula 15 or a salt thereof; FOLLOWS FORMULA 7, d) treating a compound of formula 15 or a salt thereof, wherein R1 is an amine protecting group, with a deprotecting agent to form the compound of formula 16 or a salt thereof; FOLLOWS FORMULA 8, e) treating a compound of formula 16 or a salt thereof with 6-methoxynicotinaldehyde and a reducing agent to form the compound of Formula I or a pharmaceutically acceptable salt thereof. Eleven claims follow;