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 77485ノート

反応式

HRID 77485 の反応式
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]

参加物

5

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 70681Tetrabutylammonium Chloride触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
120 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-3b60ffbaf417475496752e89f24121e9
出典データセット
uspto-grants-2014_09
特許番号
US08841301B2

反応ノート

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