Cl.[NH2:2][C@@H:3]1[C:9](=[O:10])[NH:8][C:7]2[CH:11]=[CH:12][C:13]([C:15]#[N:16])=[CH:14][C:6]=2[N:5]([C:17]([CH:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[O:18])[C@H:4]1[CH3:25].[C:26]([N:33]([CH3:39])[C@H:34]([C:36](O)=[O:37])[CH3:35])([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[C:15]([C:13]1[CH:12]=[CH:11][C:7]2[NH:8][C:9](=[O:10])[C@@H:3]([NH:2][C:36](=[O:37])[C@@H:34]([N:33]([CH3:39])[C:26](=[O:27])[O:28][C:29]([CH3:30])([CH3:32])[CH3:31])[CH3:35])[C@H:4]([CH3:25])[N:5]([C:17]([CH:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)=[O:18])[C:6]=2[CH:14]=1)#[N:16]To a 0° C. solution of (3S,4S)-3-amino-4-methyl-2-oxo-5-(tetrahydro-2H-pyran-4-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile hydrochloride (218 mg, 598 μmol) in DMF (1.99 ml) was added Boc-N-methyl-L-alanine (134 mg, 657 μmol), N,N-diisopropylethylamine (414 μl, 2.39 mmol), and HBTU (249 mg, 657 μmol). 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)-8-cyano-2-methyl-4-oxo-1-(tetrahydro-2H-pyran-4-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (239 mg, 78%) as a white solid. MS m/z 536 (MNa)+.
読み込み中…