Example 1 Preparation of 4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(dimethylcarbamoyl)-1H-indazol-3-yl)cyclohex-3-enecarboxylic acid (1A)
Step 1: Preparation of methyl 1H-indazole-6-carboxylate (A-2).
Methyl 3-amino-4-methylbenzoate (A-1) (5.0 g, 30.2 mmol) was dissolved in acetic acid (140 mL). An aqueous solution of sodium nitrite (2.1 g, 30.2 mmol) was added slowly and dropwise (3.5 mL) to the reaction mixture under cooling in an ice bath. After removing the ice bath, the reaction mixture was stirred at room temperature overnight. Upon completion of the reaction, about half of the solvent was removed by evaporation, and the remaining mixture was diluted with water (80 mL) and extracted with ethyl acetate (3 x 30 mL). The organic phases were combined, washed sequentially with water and saturated saline (2×200 mL each), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the product A-2 (4.4 g, 83% yield).
LCMS (ESI): calculated value for C9H8N2O2, [M + H]+: 177, measured value: 177.
