Tetrabutylammonium Fluoride → 1-(4-Fluoro-phenyl)-1H-indazole-4-carboxylic acid (6-ethynyl-pyridin-3-ylmethyl)-amide

Participants

Reaction Steps

To a mixture of 1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid (6-bromo-pyridin-3-ylmethyl)-amide (105 mg, 0.247 mmol), trimethylsilyl acetylene (0.105 mL, 0.741 mmol), copper(I) iodide (4.7 mg, 0.025 mmol) and Pd(PPh3)2Cl2 (8.7 mg, 0.012 mmol) was added triethylamine (1.0 mL) and anhydrous DMF (0.25 mL). After 16 hours, the mixture was diluted with diethyl ether (50 mL) and quenched with saturated aqueous ammonium chloride (50 mL). The organic layer was washed with saturated aqueous ammonium chloride (50 mL) and brine (50 mL), dried over MgSO4 and concentrated. The crude solid was purified by silica gel chromatography eluting with a gradient of 0-50% ethyl acetate in hexanes to afford 1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid (6-trimethylsilanylethynyl-pyridin-3-ylmethyl)-amide as a tan solid. 1-(4-Fluoro-phenyl)-1H-indazole-4-carboxylic acid (6-trimethylsilanylethynyl-pyridin-3-ylmethyl)-amide (70.0 mg, 0.158 mmol) was dissolved in THF (1.0 mL) and treated with a 1 M solution of TBAF in THF (0.16 mL, 0.16 mmol) at room temperature. The solution was stirred for 2 hours and then diluted with diethyl ether (10 mL) and quenched with water (10 mL). The aqueous layers were extracted with diethyl ether (3×5 mL). The combined organic layers were washed with brine (10 mL), dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography eluting with a gradient of 0-70% ethyl acetate in hexanes to afford the title compound as a white solid.

Provenance & Evidence