5-Bromo-N-methoxy-N-methylpyridine-3-carboxamide → (5-Bromo-pyridin-3-yl)-{7-[1-(tetrahydro-pyran-2-yloxymethyl)-cyclopropyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-methanone

Participants

Reaction Steps

To a stirred solution of 5-Iodo-7-[1-(tetrahydro-pyran-2-yloxymethyl)-cyclopropyl]-7H-pyrrolo[2,3-d]pyrimidine (Preparation 249, 450 mg, 1.13 mmol) in diethyl ether (6 mL) was added n-butyl lithium (2M in hexane, 0.62 mL, 1.24 mmol) drop wise at −70° C. Then a solution of 5-Bromo-N-methoxy-N-methyl-nicotinamide (304 mg, 1.24 mmol) in diethyl ether (2.5 mL) was added drop wise at −70° C. and stirred at same temperature for another 30 minutes. The reaction was allowed to warm to room temperature slowly. The reaction was quenched with saturated aqueous ammonium chloride solution (10 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layer was washed with water (20 mL), brine (20 mL), dried over sodium sulphate and evaporated in vacuo. The crude material was purified by column chromatography on silica gel (gradient of dichloromethane:methanol 100:0 to 98:2) to afford the title compound as a light brown sticky solid in 35% yield, 250 mg.

Provenance & Evidence