Diisopropylethylamine → tert-butyl(S)-1-((3S,4S)-5-acetyl-7-cyano-1-((2-methoxynaphthalen-1-yl)methyl)-4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1, 4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate

HRID 1486108노트

반응식

HRID 1486108 반응식
Cl.[C:2]([N:5]1[C@@H:11]([CH3:12])[C@H:10]([NH2:13])[C:9](=[O:14])[N:8]([CH2:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=[CH:18][C:17]=2[O:26][CH3:27])[C:7]2[CH:28]=[CH:29][C:30]([C:32]#[N:33])=[CH:31][C:6]1=2)(=[O:4])[CH3:3].[C:34]([N:41]([CH3:47])[C@H:42]([C:44](O)=[O:45])[CH3:43])([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35].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.O>[C:2]([N:5]1[C@@H:11]([CH3:12])[C@H:10]([NH:13][C:44](=[O:45])[C@@H:42]([N:41]([CH3:47])[C:34](=[O:35])[O:36][C:37]([CH3:38])([CH3:40])[CH3:39])[CH3:43])[C:9](=[O:14])[N:8]([CH2:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=[CH:18][C:17]=2[O:26][CH3:27])[C:7]2[CH:28]=[CH:29][C:30]([C:32]#[N:33])=[CH:31][C:6]1=2)(=[O:4])[CH3:3]

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 7009590(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 72712573(3S,4S)-5-acetyl-3-amino-1-((2-methoxynaphthalen-1-yl)methyl)-4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile hydrochloride

생성물 1

HCID 72712575tert-butyl(S)-1-((3S,4S)-5-acetyl-7-cyano-1-((2-methoxynaphthalen-1-yl)methyl)-4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1, 4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate수율 89.4%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

To a 0° C. solution of (3S,4S)-5-acetyl-3-amino-1-((2-methoxynaphthalen-1-yl)methyl)-4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile hydrochloride (216 mg, 465 μmol) in DMF (1.55 ml) was added Boc-N-methyl-L-alanine (104 mg, 511 μmol), N,N-diisopropylethylamine (322 μl, 1.86 mmol), and HBTU (194 mg, 511 μmol). The reaction was stirred at rt for 30 min, then diluted with H2O and the solids were collected by vacuum filtration, taken up in 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-((3S,4S)-5-acetyl-7-cyano-1-((2-methoxynaphthalen-1-yl)methyl)-4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (255 mg, 89%) as a white solid. MS m/z 636 (MNa)+.

후처리

  1. filtrationthe solids were collected by vacuum filtration
  2. washwashed with H2O, sat. aq. NaHCO3, and sat. aq. NaCl
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by flash chromatography

출처 및 근거

ORD 기록
ord-a1debe133d684275bea6c82a8d0988c7
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09422331B2

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