Diisopropylethylamine → tert-butyl(S)-1-((2S,3S)-1-acetyl-8-cyano-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate

Participants

Reaction Steps

A rt solution of tert-butyl(2S,3S)-1-acetyl-8-cyano-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate (144 mg, 402 μmol) in 4 M HCl in dioxane (2.01 ml) was stirred for 2 h. The reaction was diluted with Et2O and the solids were collected by vacuum filtration, taken up in DMF (1.34 ml), and Boc-N-methyl-L-alanine (89.9 mg, 442 μmol), N,N-diisopropylethylamine (278 μl, 1.61 mmol), and HBTU (168 mg, 442 μmol) were added at 0° C. The reaction was stirred at rt for 30 min, then diluted with EtOAc, washed with H2O, sat. aq. NaHCO3, and sat. aq. NaCl, dried over Na2SO4, filtered, and concentrated. The crude material was purified by flash chromatography to provide tert-butyl(S)-1-((2S,3S)-1-acetyl-8-cyano-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (123 mg, 69%) as a white solid. MS m/z 466 (MNa)+.

Provenance & Evidence