Methylamine → HCID 67240730, compound

Participants

Reaction Steps

A stirred solution of (2R,4R)-1-(tert-butoxycarbonyl)-4-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)piperidine-2-carboxylic acid (5.35 g, 9.80 mmol) in THF (50 ml) was cooled to −15° C. (acetone/ice). NMM (1.49 ml, 14.9 mmol) was added to the solution followed by IBCF (2.0 ml, 12.75 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 a 2.0M solution of methylamine in THF (10 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 (2R,4R)-4-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)-2-[(methylamino)carbonyl]piperidine-1-carboxylate (5.94 g, 100%) as a pale yellow foam which was used without further purification; Mass Spectrum: (M+H)+ 560.1.

Provenance & Evidence