Sodium hydride → HCID 117675493, compound

Participants

Reaction Steps

To a mixture of tert-butyl (3R)-3-hydroxypyrrolidine-1-carboxylate (860 mg) and N,N-dimethylformamide (30 mL) was added 55% oily sodium hydride (200 mg) under ice-cooling. After stirring for 30 minutes under ice-cooling, 5-chloro-6-ethyl-3-({3-methyl-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazine-2-carboxamide (1 g) was added thereto, followed by further stirring for 1 hour under ice-cooling. 55% oily sodium hydride (100 mg) was added thereto, followed by stirring at room temperature for 4 hours, and then 55% oily sodium hydride (100 mg) was added thereto, followed by stirring at room temperature overnight. The reaction mixture was poured into ice water, followed by extraction with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-100:10:1) to obtain tert-butyl (3R)-3-{[5-carbamoyl-3-ethyl-6-({3-methyl-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazin-2-yl]oxy}pyrrolidine-1-carboxylate (284 mg).

Provenance & Evidence