Diisopropylethylamine → tert-butyl(S)-1-((2S,3S)-1-acetyl-8-cyano-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate

HRID 1486089노트

반응식

HRID 1486089 반응식
[C:1]([N:4]1[C@@H:10]([CH3:11])[C@H:9]([NH:12][C:13](=[O:19])OC(C)(C)C)[C:8](=[O:20])[NH:7][C:6]2[CH:21]=[CH:22][C:23]([C:25]#[N:26])=[CH:24][C:5]1=2)(=[O:3])[CH3:2].[C:27]([N:34]([CH3:40])[C@H:35](C(O)=O)[CH3:36])([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28].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>Cl.O1CCOCC1.CCOCC.CCOC(C)=O>[C:1]([N:4]1[C@@H:10]([CH3:11])[C@H:9]([NH:12][C:13](=[O:19])[C@@H:35]([N:34]([CH3:40])[C:27](=[O:28])[O:29][C:30]([CH3:32])([CH3:31])[CH3:33])[CH3:36])[C:8](=[O:20])[NH:7][C:6]2[CH:21]=[CH:22][C:23]([C:25]#[N:26])=[CH:24][C:5]1=2)(=[O:3])[CH3:2]

참가 물질

9

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 131736779tert-butyl(2S,3S)-1-acetyl-8-cyano-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate

생성물 1

HCID 90088957tert-butyl(S)-1-((2S,3S)-1-acetyl-8-cyano-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate수율 69%

시약·촉매·용매 4

HCID 313Hydrochloric Acid용매HCID 3283Diethyl Ether용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

A rt solution of tert-butyl(2S,3S)-1-acetyl-8-cyano-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate (144 mg, 402 μmol) in 4 M HCl in dioxane (2.01 ml) was stirred for 2 h. The reaction was diluted with Et2O and the solids were collected by vacuum filtration, taken up in DMF (1.34 ml), and Boc-N-methyl-L-alanine (89.9 mg, 442 μmol), N,N-diisopropylethylamine (278 μl, 1.61 mmol), and HBTU (168 mg, 442 μmol) were added at 0° C. 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)-1-acetyl-8-cyano-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (123 mg, 69%) as a white solid. MS m/z 466 (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-86b18467d4bd4c968caad427cf8768f5
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09422331B2

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