反应详情

To a stirred solution of N-tert-butyl-2-(5-(difluoromethoxy)-1-(morpholin-2-ylmethyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (100 mg, 159 μmol) in methanol (4 mL), cooled to 0° C. with ice bath, was added aqueous formaldehyde (1 mL, 13.4 mmol), followed by the addition of sodium triacetoxyborohydride (75.7 mg, 357 μmol). The reaction mixture was stirred at room temperature for 15 h then concentrated in vacuo. Purification by chromatography (silica, 4 g Analogix column, 0-10% methanol containing 10% ammonium hydroxide in dichloromethane) gave N-tert-butyl-2-(5-(difluoromethoxy)-1-(4-methylmorpholin-2-yl)methyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (63 mg, 62%). MS (M+H)+=644.

1. concentrationthen concentrated in vacuo
2. customPurification by chromatography (silica, 4 g Analogix column, 0-10% methanol containing 10% ammonium hydroxide in dichloromethane)