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 093a, the process comprising:

• (1) forming compound 181a by step 1 comprising forming a reaction mixture comprising compound 339, a source of Br, optionally a photo- or thermally sensitive radical initiator, and a solvent system, and reacting the reaction mixture under photochemical conditions to form a reaction product mixture comprising compound 181a according to the following reaction scheme
• (2) forming compound 378 by the (i) the combination of steps 2(a) and 2(b) or by (ii) step 2,
• (i) wherein step 2(a) comprises forming a reaction mixture comprising compound 181a, a base, and a solvent system, and reacting the reaction mixture to form a reaction product mixture comprising compound 050 according to the following reaction scheme
• and
• wherein step 2(b) comprises forming a reaction mixture comprising compound 050, an oxidizing reagent, a phase transfer catalyst, and a solvent system, and reacting the reaction mixture to form a reaction product mixture comprising compound 378 according to the following reaction scheme
• and
• (ii) wherein step 2 comprises forming a reaction mixture comprising compound 181a, an oxidizing reagent, and a solvent system, and reacting the reaction mixture to form a reaction product mixture comprising compound 378 according to the following reaction scheme
• (3) forming compound 003a by step 3 comprising forming a reaction mixture comprising compound 378, 3-aminopyridine, an acid catalyst, and a solvent system, and reacting the reaction mixture to form a reaction product mixture comprising compound 003a according to the following
• and
• (4) forming compound 093a by step 4 comprising forming a reaction mixture comprising compound 003a, a phosphine or a phosphite, and a solvent system, and reacting the reaction mixture to form a reaction product mixture comprising compound 093a according to the following reaction scheme
• wherein the phosphine is selected from tri (C1-4) alkyl phosphine and triaryl phosphine and the phosphite is selected from tri (C1-4) alkyl phosphite and triaryl phosphite.