反应详情

To a stirred solution of {(S)-1-[(S)-1-(6-bromo-2-methoxy-naphthalen-1-ylmethyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl ester (Intermediate 11) (300 mg, 0.49 mmol) in THF (10.0 mL) was added Cs2CO3 (320 mg, 0.98 mmol) and stirred at RT for 3 h. The mixture was cooled to 0° C., isophthaloyl dichloride (49 mg, 0.24 mmol) was added, the cooling bath was removed and the mixture was stirred at RT. After 18 h, the mixture was diluted with ethyl acetate, washed with water and brine. The organic layer was evaporated and the residue purified by preparative reverse phase HPLC to afford tert-butyl N-[(1S)-2-[[(3S)-5-[(6-bromo-2-methoxy-1-naphthyl)methyl]-1-[3-[(3S)-5-[(6-bromo-2-methoxy-1-naphthyl)methyl]-3-[[(2S)-2-[tert-butoxycarbonyl(methyl)amino]propanoyl]amino]-4-oxo-2,3-dihydro-1,5-benzodiazepine-1-carbonyl]benzoyl]-4-oxo-2,3-dihydro-1,5-benzodiazepin-3-yl]amino]-1-methyl-2-oxo-ethyl]-N-methyl-carbamate (18 mg, 3%). LC-MS: 1353.8 (M+H), 1370.8 (M+NH4).

1. temperatureThe mixture was cooled to 0° C.
2. customthe cooling bath was removed
3. stirringthe mixture was stirred at RT
4. waitAfter 18 h
5. additionthe mixture was diluted with ethyl acetate
6. washwashed with water and brine
7. customThe organic layer was evaporated
8. customthe residue purified by preparative reverse phase HPLC