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

HRID 1486093노트

반응식

HRID 1486093 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:27])[C@@H:16]([N:18]([CH3:26])[C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH3:17])[C@H:9]([CH3:28])[N:8]([C:29](=[O:35])[CH2:30][S:31]([CH3:34])(=[O:33])=[O:32])[C:7]=2[CH:36]=1)#[N:2].[Br:37][C:38]1[CH:47]=[CH:46][CH:45]=[C:44]2[C:39]=1[CH:40]=[CH:41][C:42]([O:50][CH3:51])=[C:43]2[CH2:48]Cl.C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[Na+]>CN(C=O)C.CCOC(C)=O>[Br:37][C:38]1[CH:47]=[CH:46][CH:45]=[C:44]2[C:39]=1[CH:40]=[CH:41][C:42]([O:50][CH3:51])=[C:43]2[CH2:48][N:12]1[C:11](=[O:13])[C@@H:10]([NH:14][C:15](=[O:27])[C@@H:16]([N:18]([CH3:26])[C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:22])[CH3:23])[CH3:17])[C@H:9]([CH3:28])[N:8]([C:29](=[O:35])[CH2:30][S:31]([CH3:34])(=[O:32])=[O:33])[C:7]2[CH:36]=[C:3]([C:1]#[N:2])[CH:4]=[CH:5][C:6]1=2

참가 물질

7

반응물 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 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)carbamateHCID 899225115-Bromo-1-(chloromethyl)-2-methoxynaphthalene

생성물 1

HCID 118292656tert-butyl(S)-1-((3S,4S)-1-((5-bromo-2-methoxynaphthalen-1-yl)methyl)-7-cyano-4-methyl-5-(2-(methylsulfonyl)acetyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate수율 76%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To a rt solution of 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 (29.5 mg, 56.6 μmol) in DMF (141 μl) was added 5-bromo-1-(chloromethyl)-2-methoxynaphthalene (17.8 mg, 62.2 μmol), cesium carbonate (22.1 mg, 67.9 μmol), and sodium iodide (10.2 mg, 67.9 μmol). The reaction was stirred at rt for 2.5 h, then diluted with EtOAc, washed with H2O 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)-1-((5-bromo-2-methoxynaphthalen-1-yl)methyl)-7-cyano-4-methyl-5-(2-(methylsulfonyl)acetyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (33 mg, 76%) as a white solid. MS m/z 792/794 (MNa)+.

후처리

  1. washwashed with H2O 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-245cb6f3e0e14515af6fad83624ac4b4
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09422331B2

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