1,2-Dichloroethane → (R)-1-(4-(3-fluoro-4-(7-methoxyquinolin-4-yloxy)phenylcarbamoyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydropyrazol-1-yl)propan-2-yl 2-((benzyloxycarbonyl)(methyl)-amino)acetate

HRID 1517828노트

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HRID 1517828 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]([N:51]([CH2:53][C:54](O)=[O:55])[CH3:52])([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>[CH2:44]([O:43][C:41]([N:51]([CH3:52])[CH2:53][C:54]([O:33][C@H:31]([CH3:32])[CH2:30][N:27]1[C:28]([CH3:29])=[C:24]([C:22](=[O:23])[NH:21][C:4]2[CH:5]=[CH:6][C:7]([O:8][C:9]3[C:18]4[C:13](=[CH:14][C:15]([O:19][CH3:20])=[CH:16][CH:17]=4)[N:12]=[CH:11][CH:10]=3)=[C:2]([F:1])[CH:3]=2)[C:25](=[O:40])[N:26]1[C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)=[O:55])=[O:42])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1

참가 물질

6

반응물 3

HCID 111,2-DichloroethaneHCID 97053N-CarbobenzoxysarcosineHCID 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 66670738(R)-1-(4-(3-fluoro-4-(7-methoxyquinolin-4-yloxy)phenylcarbamoyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydropyrazol-1-yl)propan-2-yl 2-((benzyloxycarbonyl)(methyl)-amino)acetate수율 84%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매2회

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온도
0 °C

실험 절차

To a mixture of (R)—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), N-Cbz-sarcosine (1.643 g, 7.36 mmol) and DMAP (0.9 g, 7.36 mmol, Aladdin) in 15 mL of CH2Cl2 was added EDC solid (1.06 g, 5.52 mmol, Aladdin) in portions at 0° C. After stirring at 0° C. for 2 hrs, the reaction mixture was warmed up to room temperature, and continued to stir at rt overnight. The mixture was diluted with 100 mL of CH2Cl2 and the resulted solution was washed with 0.1 N HCl (10 mL×2), followed by saturated NaHCO3 solution (20 mL×2) and water (20 mL). The aqueous phase was extracted with EtOAc (50 mL×3), and the combined organic phases were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by a silica gel column chromatography (EtOAc/hexane=2/1) to give the desired compound as a pale yellow solid (2.31 g, 84%).

후처리

  1. temperaturethe reaction mixture was warmed up to room temperature
  2. stirringto stir at rt overnight
  3. washthe resulted solution was washed with 0.1 N HCl (10 mL×2)
  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/hexane=2/1)

출처 및 근거

ORD 기록
ord-eac451f795034ee18e925c3c7feb03ff
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08232294B2

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