Sodium Iodide → tert-butyl(S)-1-((3S,4S)-1-((2-chloro-3-methylquinolin-4-yl)methyl)-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 1486055ノート

反応式

HRID 1486055 の反応式
[Cl:1][C:2]1[C:11]([CH3:12])=[C:10]([CH2:13]O)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.[CH3:27][N:28]([C@@H:36]([CH3:60])[C:37]([NH:39][C@H:40]1[C@H:46]([CH3:47])[N:45]([C:48](=[O:54])[CH2:49][S:50]([CH3:53])(=[O:52])=[O:51])[C:44]2[CH:55]=[CH:56][CH:57]=[CH:58][C:43]=2[NH:42][C:41]1=[O:59])=[O:38])[C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32].C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[Na+]>C(Cl)Cl.CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[C:11]([CH3:12])=[C:10]([CH2:13][N:42]2[C:41](=[O:59])[C@@H:40]([NH:39][C:37](=[O:38])[C@@H:36]([N:28]([CH3:27])[C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:32])[CH3:33])[CH3:60])[C@H:46]([CH3:47])[N:45]([C:48](=[O:54])[CH2:49][S:50]([CH3:53])(=[O:52])=[O:51])[C:44]3[CH:55]=[CH:56][CH:57]=[CH:58][C:43]2=3)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1

参加物

10

反応物 6

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 10796Cesium carbonateHCID 31297Methanesulfonyl chlorideHCID 89923521(2-Chloro-3-methylquinolin-4-yl)methanolHCID 90082560tert-butyl methyl((S)-1-((2S,3S)-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)carbamate

生成物 1

HCID 118292663tert-butyl(S)-1-((3S,4S)-1-((2-chloro-3-methylquinolin-4-yl)methyl)-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 45.4%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

To a rt suspension of (2-chloro-3-methylquinolin-4-yl)methanol (61 mg, 294 μmol) in CH2Cl2 (2.94 ml) was added triethylamine (81.9 μl, 588 μmol), followed by methanesulfonyl chloride (27.3 μl, 353 μmol), dropwise. The reaction was stirred at rt for 1.5 h, then diluted with CH2Cl2, washed with H2O and sat. aq. NaCl, dried over Na2SO4, filtered, and concentrated. This material was mixed with tert-butyl methyl((S)-1-((2S,3S)-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)carbamate (100 mg, 201 μmol), cesium carbonate (85.3 mg, 262 μmol), and sodium iodide (39.2 mg, 262 μmol) in DMF (503 μl). The reaction was stirred at rt for 16 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-((2-chloro-3-methylquinolin-4-yl)methyl)-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 (62.6 mg, 45%) as a white solid. MS m/z 708 (MNa)+.

後処理

  1. washwashed with H2O and sat. aq. NaCl
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. stirringThe reaction was stirred at rt for 16 h
  6. washwashed with H2O and sat. aq. NaCl
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude material was purified by flash chromatography

出典と根拠

ORDレコード
ord-18acdcd93776476ab207ced07b242373
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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