Ammonia → HCID 58318668, compound

Participants

Reaction Steps

A stirred solution of (2S,4S)-1-(tert-butoxycarbonyl)-4-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)piperidine-2-carboxylic acid (3) (5 g, 9.16 mmol) in THF (50 ml) was cooled to −15° C. (acetone/ice). NMM (1.5 ml, 13.7 mmol) was added to the solution followed by IBCF (1.54 ml, 11.9 mmol). The reaction mixture was held at −15° C. (the formation of the mixed anhydride was monitored by TLC (THF)). After 5-10 minutes, the reaction mixture was treated with concentrated aqueous ammonia (3 ml) at −15° C. and allowed to warm to room temperature. The reaction mixture was diluted with DCM (250 ml), washed with water (2×20 ml) and concentrated to give tert-butyl (2S,4S)-2-(aminocarbonyl)-4-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)piperidine-1-carboxylate (4) (5 g, 100%) as a pale yellow foam which was used without further purification; Mass Spectrum: (M+H)+ 546.1.

Provenance & Evidence