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

HRID 1486086노트

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HRID 1486086 반응식
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[NH:12][C:11](=[O:13])[C@@H:10]([NH:14][C:15](=[O:21])OC(C)(C)C)[C@H:9]([CH3:22])[N:8]([C:23](=[O:29])[CH2:24][S:25]([CH3:28])(=[O:27])=[O:26])[C:7]=2[CH:30]=1)#[N:2].[C:31]([N:38]([CH3:44])[C@H:39](C(O)=O)[CH3:40])([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32].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.CN(C=O)C.CCOC(C)=O>[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[NH:12][C:11](=[O:13])[C@@H:10]([NH:14][C:15](=[O:21])[C@@H:39]([N:38]([CH3:44])[C:31](=[O:32])[O:33][C:34]([CH3:36])([CH3:35])[CH3:37])[CH3:40])[C@H:9]([CH3:22])[N:8]([C:23](=[O:29])[CH2:24][S:25]([CH3:28])(=[O:26])=[O:27])[C:7]=2[CH:30]=1)#[N: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 72713839tert-butyl(2S,3S)-8-cyano-2-methyl-1-(2-(methylsulfonyl)acetyl)-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate

생성물 1

HCID 72713840tert-butyl(S)-1-((2S,3S)-8-cyano-2-methyl-1-(2-(methylsulfonyl)acetyl)-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate수율 74.4%

시약·촉매·용매 4

HCID 313Hydrochloric Acid용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

A rt solution of tert-butyl(2S,3S)-8-cyano-2-methyl-1-(2-(methylsulfonyl)acetyl)-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate (137 mg, 314 μmol) in 4 M HCl in dioxane (1.57 ml) was stirred for 2 h. The reaction was concentrated, taken up in in DMF (1.05 ml), and Boc-N-methyl-L-alanine (70.2 mg, 345 μmol), N,N-diisopropylethylamine (217 μl, 1.26 mmol), and HBTU (131 mg, 345 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)-8-cyano-2-methyl-1-(2-(methylsulfonyl)acetyl)-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (121.8 mg, 74%) as a white solid. MS m/z 544 (MNa)+.

후처리

  1. concentrationThe reaction was concentrated
  2. additionwere added at 0° C
  3. washwashed with H2O, sat. aq. NaHCO3, and sat. aq. NaCl
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by flash chromatography

출처 및 근거

ORD 기록
ord-e4f7efff0dff4a16b10709ccdd2e6553
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09422331B2

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