1,2-Dichloroethane → (S)-((S)-1-(4-(3-fluoro-4-(7-methoxyquinolin-4-yloxy)phenyl-carbamoyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydropyrazol-1-yl)propan-2-yl)2-(benzyloxycarbonylamino)propanoate

HRID 1517815ノート

反応式

HRID 1517815 の反応式
[F:1][C:2]1[CH:3]=[C:4]([NH:21][C:22]([C:24]2[C:25](=[O:40])[N:26]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[N:27]([CH2:30][CH:31]([OH:33])[CH3:32])[C:28]=2[CH3:29])=[O:23])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([O:19][CH3:20])=[CH:16][CH:17]=2)[N:12]=[CH:11][CH:10]=1.[C:41]([NH:51][C@H:52]([C:54](O)=[O:55])[CH3:53])([O:43][CH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)=[O:42].C(Cl)CCl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([NH:21][C:22]([C:24]2[C:25](=[O:40])[N:26]([C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)[N:27]([CH2:30][C@@H:31]([O:33][C:54](=[O:55])[C@@H:52]([NH:51][C:41]([O:43][CH2:44][C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)=[O:42])[CH3:53])[CH3:32])[C:28]=2[CH3:29])=[O:23])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([O:19][CH3:20])=[CH:16][CH:17]=2)[N:12]=[CH:11][CH:10]=1

参加物

6

反応物 3

HCID 111,2-DichloroethaneHCID 736104N-carbobenzyloxyalanineHCID 595983963-fluoro-4-(7-methoxyquinolin-4-yloxy)-phenyl-1-(2-hydroxypropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

生成物 1

HCID 66670623(S)-((S)-1-(4-(3-fluoro-4-(7-methoxyquinolin-4-yloxy)phenyl-carbamoyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydropyrazol-1-yl)propan-2-yl)2-(benzyloxycarbonylamino)propanoate収率 76.3%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒2 回

反応条件

温度
0 °C

実験手順

To a solution of (S)—N-(3-fluoro-4-(7-methoxyquinolin-4-yloxy)phenyl-1-(2-hydroxypropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (2.0 g, 3.68 mmol), (S)—N-Cbz-alanine (1.647 g, 7.36 mmol, Shanghai Hanhong Chemical CO., LTD.) and DMAP (0.90 g, 7.36 mmol, Aladdin) in 30 mL of CH2Cl2 at 0° C. was added EDC solid (2.116 g, 11.04 mmol, Aladdin) in portions. The mixture was continued to stir at 0° C. for 2 hrs, and then the reaction mixture was warmed up to room temperature, and stirred at rt for 20 hrs. The mixture was diluted with 180 mL CH2Cl2, and the result solution was washed with 0.1 N HCl (10 mL×3), followed by 50 mL saturated NaHCO3. The aqueous phase was extracted with EtOAc (50 mL×3), the combined organic phases were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by a silica gel column chromatography (EtOAc) to give the desired compound as a pale yellow solid (2.1 g, 73%).

後処理

  1. temperaturethe reaction mixture was warmed up to room temperature
  2. stirringstirred at rt for 20 hrs
  3. washthe result solution was washed with 0.1 N HCl (10 mL×3)
  4. extractionThe aqueous phase was extracted with EtOAc (50 mL×3)
  5. dry with materialthe combined organic phases were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by a silica gel column chromatography (EtOAc)

出典と根拠

ORDレコード
ord-fd9de845907446458bd0bd0b1dded22e
出典データセット
uspto-grants-2012_07
特許番号
US08232294B2

反応ノート

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