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 1517815노트

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HRID 1517815 반응식
[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

참가 물질

6

반응물 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

생성물 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)propanoate수율 76.3%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매2회

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온도
0 °C

실험 절차

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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-fd9de845907446458bd0bd0b1dded22e
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08232294B2

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