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 1486093ノート

反応式

HRID 1486093 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: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

参加物

7

反応物 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

生成物 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)carbamate収率 76%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-245cb6f3e0e14515af6fad83624ac4b4
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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