5-bromo-N-(3-chloro-4-(difluoromethoxy)phenyl)pyrimidin-2-amine → (E)-6-(2-(2-(3-chloro-4-(difluoromethoxy)phenylamino)pyrimidin-5-yl)vinyl)-1-((2-(trimethylsilyl)ethoxy)methyl)quinolin-2(1H)-one

HRID 77485노트

반응식

HRID 77485 반응식
Br[C:2]1[CH:3]=[N:4][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH:16]([F:18])[F:17])=[C:11]([Cl:19])[CH:10]=2)=[N:6][CH:7]=1.[CH3:20][Si:21]([CH3:40])([CH3:39])[CH2:22][CH2:23][O:24][CH2:25][N:26]1[C:35]2[C:30](=[CH:31][C:32]([CH:36]=[CH2:37])=[CH:33][CH:34]=2)[CH:29]=[CH:28][C:27]1=[O:38]>CN(C=O)C.[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:19][C:11]1[CH:10]=[C:9]([NH:8][C:5]2[N:4]=[CH:3][C:2](/[CH:37]=[CH:36]/[C:32]3[CH:31]=[C:30]4[C:35](=[CH:34][CH:33]=3)[N:26]([CH2:25][O:24][CH2:23][CH2:22][Si:21]([CH3:20])([CH3:40])[CH3:39])[C:27](=[O:38])[CH:28]=[CH:29]4)=[CH:7][N:6]=2)[CH:14]=[CH:13][C:12]=1[O:15][CH:16]([F:18])[F:17]

참가 물질

5

반응물 2

HCID 866797715-bromo-N-(3-chloro-4-(difluoromethoxy)phenyl)pyrimidin-2-amineHCID 866797751-((2-(trimethylsilyl)ethoxy)methyl)-6-vinylquinolin-2(1H)-one

생성물 1

HCID 86679777(E)-6-(2-(2-(3-chloro-4-(difluoromethoxy)phenylamino)pyrimidin-5-yl)vinyl)-1-((2-(trimethylsilyl)ethoxy)methyl)quinolin-2(1H)-one수율 49.1%

시약·촉매·용매 2

HCID 70681Tetrabutylammonium Chloride촉매HCID 6228Dimethylformamide용매

반응 조건

온도
120 °C

실험 절차

To a solution of 5-bromo-N-(3-chloro-4-(difluoromethoxy)phenyl)pyrimidin-2-amine (0.3 g, 0.856 mmol) in DMF (5 mL), were added 1-((2-(trimethylsilyl)ethoxy)methyl)-6-vinylquinolin-2(1H)-one (0.258 g, 0.856 mmol) triethylamine (0.358 mL, 2.57 mmol), tetrabutylammonium chloride, hydrate (0.380 g, 1.284 mmol) and PdOAc2 (0.019 g, 0.086 mmol). The reaction mixture was heated at 120° C. for 12 h. The reaction mixture was concentrated, dissolved in ethyl acetate, filtered through celite, and washed with water. The organic layer was dried over anhydrous sodium sulfate, concentrated and purified by flash chromatography on silica gel using 15% ethyl acetate in petroleum ether to give (E)-6-(2-(2-(3-chloro-4-(difluoromethoxy)phenylamino)pyrimidin-5-yl)vinyl)-1-((2-(trimethylsilyl)ethoxy)methyl)quinolin-2(1H)-one (0.24 g, 49%). LCMS (ES-API), RT: 2.56 m/z 571.2 (M+H).

후처리

  1. concentrationThe reaction mixture was concentrated
  2. dissolutiondissolved in ethyl acetate
  3. filtrationfiltered through celite
  4. washwashed with water
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. custompurified by flash chromatography on silica gel using 15% ethyl acetate in petroleum ether

출처 및 근거

ORD 기록
ord-3b60ffbaf417475496752e89f24121e9
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08841301B2

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