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 1486086ノート

反応式

HRID 1486086 の反応式
[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]

参加物

9

反応物 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

生成物 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)carbamate収率 74.4%

試薬・触媒・溶媒 4

HCID 313Hydrochloric Acid溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-e4f7efff0dff4a16b10709ccdd2e6553
出典データセット
uspto-grants-2016_08
特許番号
US09422331B2

反応ノート

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