1-Methylimidazole → Tert-butyl ((3S,4S)-7-cyano-4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[B][1,4]diazepin-3-YL)carbamate

Participants

Reaction Conditions

Reaction Steps

A mixture of (2S,3S)-3-(2-amino-5-cyanophenylamino)-2-(tert-butoxycarbonylamino)butanoic acid (4.9 g, 14.7 mmol) in acetonitrile (96 ml), was cooled in an ice water bath, then 1-methylimidazole (3.5 ml, 44.0 mmol) was added and the reaction was stirred at 0° C. for 20 min, then methanesulfonyl chloride (1.31 ml, 16.9 mmol) was added dropwise. The cooling bath was removed and the reaction was stirred at RT for 2 h, then concentrated to 13 volume and treated with water (˜200 ml, dropwise addition). The resulting solid was separated by filtration, washed with H2O, and dried under vacuum at 50° C. for 3 h to afford tert-butyl(3S,4S)-7-cyano-4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate (4.2 g). The aqueous solution was extracted with EtOAc, dried over Na2SO4, and purified by flash chromatography (0-60% EtOAc in DCM) to afford additional product (0.4 g). MS m/z 339 (MNa)+.

Provenance & Evidence