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

HRID 1486115
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HRID 1486115 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[CH3:26])[C:7]2[CH:27]=[CH:28][C:29]([C:31]#[N:32])=[CH:30][C:6]1=2)(=[O:4])[CH3:3].[C:33]([N:40]([CH3:46])[C@H:41]([C:43](O)=[O:44])[CH3:42])([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34].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:43](=[O:44])[C@@H:41]([N:40]([CH3:46])[C:33](=[O:34])[O:35][C:36]([CH3:37])([CH3:39])[CH3:38])[CH3:42])[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[CH3:26])[C:7]2[CH:27]=[CH:28][C:29]([C:31]#[N:32])=[CH:30][C:6]1=2)(=[O:4])[CH3:3]
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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 72712775(3S,4S)-5-acetyl-3-amino-4-methyl-1-((2-methylnaphthalen-1-yl)methyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile hydrochloride

생성물 1

HCID 72712777
tert-butyl(S)-1-((3S,4S)-5-acetyl-7-cyano-4-methyl-1-((2-methylnaphthalen-1-yl)methyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate
수율 88%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

To a 0° C. solution of (3S,4S)-5-acetyl-3-amino-4-methyl-1-((2-methylnaphthalen-1-yl)methyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile hydrochloride (162 mg, 361 μmol) in DMF (1.2 ml) was added Boc-N-methyl-L-alanine (80.7 mg, 397 μmol), N,N-diisopropylethylamine (250 μl, 1.44 mmol), and HBTU (151 mg, 397 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-4-methyl-1-((2-methylnaphthalen-1-yl)methyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (189 mg, 88%) as a white solid. MS m/z 620 (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-ca0cbe5a0a4c4aa8a63716fdef1cbbc0
출처 데이터셋
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09422331B2

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