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Diisopropylethylamine → 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

HRID 1486092
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HRID 1486092 반응식
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]
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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 90082569(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

생성물 1

HCID 90089030
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
수율 78%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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)+.

후처리

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

출처 및 근거

ORD 기록
ord-b8d93b17ce5d47a3959a09c08438d16a
출처 데이터셋
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09422331B2

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