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

HRID 1486110ノート

反応式

HRID 1486110 の反応式
[C:1]([N:4]1[C@@H:10]([CH3:11])[C@H:9]([NH:12][C:13](=[O:25])[C@@H:14]([N:16]([CH3:24])[C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH3:15])[C:8](=[O:26])[NH:7][C:6]2[CH:27]=[CH:28][C:29]([C:31]#[N:32])=[CH:30][C:5]1=2)(=[O:3])[CH3:2].Cl[CH2:34][C:35]1[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH:38]=[CH:37][C:36]=1[CH3:45].C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[Na+]>CN(C=O)C.CCOC(C)=O>[C:1]([N:4]1[C@@H:10]([CH3:11])[C@H:9]([NH:12][C:13](=[O:25])[C@@H:14]([N:16]([CH3:24])[C:17](=[O:23])[O:18][C:19]([CH3:21])([CH3:20])[CH3:22])[CH3:15])[C:8](=[O:26])[N:7]([CH2:34][C:35]2[C:44]3[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=3)[CH:38]=[CH:37][C:36]=2[CH3:45])[C:6]2[CH:27]=[CH:28][C:29]([C:31]#[N:32])=[CH:30][C:5]1=2)(=[O:3])[CH3:2]

参加物

7

反応物 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 811061-Chloromethyl-2-methylnaphthaleneHCID 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)carbamate

生成物 1

HCID 72712777tert-butyl(S)-1-((3S,4S)-5-acetyl-7-cyano-4-methyl-1-((2-methylnaphthalen-1-yl)methyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate収率 73%

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)-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 (57 mg, 129 μmol) in DMF (321 μl) was added 1-(chloromethyl)-2-methylnaphthalene (29.4 mg, 154 μmol), cesium carbonate (54.4 mg, 167 μmol), and sodium iodide (25.0 mg, 167 μmol). The reaction was stirred at rt for 1 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)-5-acetyl-7-cyano-4-methyl-1-((2-methylnaphthalen-1-yl)methyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (56.3 mg, 73%) as a white solid. MS m/z 620 (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-5591c39c042e486da22b901cd9771e9b
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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