Processes for the preparation of n-(1-methylcyclopropyl)-2-(3-pyridinyl)-2h-indazole-4-carboxamide and intermediates thereof

A process for the preparation of compound 200 according to a first scheme, a second scheme, or a third scheme, wherein:

• (1) the first scheme for preparing compound 200 comprises
• (i) step 1 comprising forming a reaction mixture comprising compound 775, HCl, and a solvent system, and reacting the reaction mixture to form a reaction product mixture comprising compound 069 according to the following reaction scheme
• (ii) step 2 comprising forming a reaction mixture comprising compound 069, a base, and a solvent system, and reacting the reaction mixture to form a reaction product mixture comprising compound 079 according to the following reaction scheme
• and
• (iii) step 3 comprising forming a reaction mixture comprising compound 079, an oxidizing agent, optionally a base, and a solvent system, and reacting the reaction mixture to form a reaction product mixture comprising compound 200 according to the following reaction scheme
• (2) the second scheme for preparing compound 200 comprises
• (i) step 1 comprising forming a reaction mixture comprising compound 900, CHCX3, a base, a solvent system, and a phase transfer catalyst, and reacting the reaction mixture to form a reaction product mixture comprising compound 905 according to the following reaction scheme
• wherein R is selected from the group consisting of COOCH3, COOCH2CH3, COOH, and CN, and
• wherein each X is independently selected from the group consisting of Cl, Br, and I, with the proviso that when
• (ii) when R is COOCH3, COOCH2CH3, or CN, the process further comprises step 1b comprising forming a reaction mixture comprising compound 905, a base, and a solvent system, and reacting the reaction mixture to form a reaction product mixture comprising compound 906 according to the following reaction scheme
• (iii) step 2 comprising forming a reaction mixture comprising compound 906, a reducing agent, and a solvent system, and reacting the reaction mixture to form a reaction product mixture comprising compound 200 according to the following reaction scheme
• with the proviso that when R is COOH, the process comprises step 2′ comprising forming a reaction mixture comprising compound 905, a reducing agent, and a solvent system, and reacting the reaction mixture to form a reaction product mixture comprising compound 200 according to the following scheme
• (3) the third scheme for preparing compound 200 comprises
• (i) step 1 comprising forming a reaction mixture comprising acetic acid, compound 100a solvent system, a base, a photocatalyst, and a solvent system, and reacting the reaction mixture by exposure to light emitted from at least one light emitting source to form a reaction product mixture comprising compound 110 according to the following reaction scheme
• (ii) step 2 comprising forming a reaction mixture comprising compound 110, a solvent system, and a base, and reacting the reaction mixture to form a reaction product mixture comprising compound 200 according to the following reaction scheme

A process for preparing compound 070, the process comprising a first and a second scheme;

• the first scheme comprising:
• (1) step 1 comprising substep (a) comprising forming a reaction mixture comprising compound 200, a chlorinating reagent, and a solvent system and reacting the reaction mixture to form a reaction product mixture comprising an acid chloride intermediate, followed by substep (b) comprising forming a reaction mixture by combining the reaction product mixture from substep (a) with an ammonia source and reacting the reaction mixture to form a reaction product mixture comprising compound 144 according to the following reaction scheme
• and
• (2) step 2 comprising substep (a) comprising forming a reaction mixture comprising compound 144, a base, an oxidant, and a solvent system, and reacting the reaction mixture to form a reaction product mixture comprising a N-halocarboxamide intermediate, followed by substep (b) comprising heating the reaction product mixture comprising the N-halocarboxamide intermediate to form a reaction product mixture comprising compound 070 according to the following reaction scheme
• the second scheme comprising:
• (1) step 1 comprising forming a reaction mixture comprising compound 900, CHCX3, a base, a solvent system, and a phase transfer catalyst, and reacting the reaction mixture to form a reaction product mixture comprising compound 905 according to the following reaction scheme
• wherein
• R is CONH2;
• and
• wherein each X is independently selected from Cl, Br, and I;
• and
• (2) step 2 comprising forming a reaction mixture comprising compound 905, a reducing agent, and a solvent system, and reacting the reaction mixture to form a reaction product mixture comprising compound 144 according to the following reaction scheme
• and
• (3) step 3 comprising forming a reaction mixture comprising compound 144, a base, an oxidant, and a solvent system, and reacting the reaction mixture to form a reaction product mixture comprising a N-halocarboxamide intermediate, followed comprising heating the reaction product mixture comprising the N-halocarboxamide intermediate to form a reaction product mixture comprising compound 070 according to the following reaction scheme

A process for the preparation of compound 070, the process comprising:

• (1) step 1 comprising forming a reaction mixture comprising compound 079, a source of hydroxyl amine, a base, and a solvent system, and reacting the reaction mixture to form a reaction product mixture comprising compound 994 according to the following reaction scheme
• (2) step 2 comprising forming a reaction mixture comprising compound 994, an activator, and a solvent system, and reacting the reaction mixture to form a reaction product mixture comprising compound 403 according to the following reaction scheme
• and
• (3) step 3 comprising forming a reaction mixture comprising compound 403, an acid, and a solvent system, and reacting the reaction mixture to form a reaction product mixture comprising compound 070 according to the following reaction scheme