Water → N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({2-[(cyclopentylmethyl)(ethyl)amino]-5-(trifluoromethyl)phenyl}methyl)-5-[2-(methylthio)ethoxy]pyrimidin-2-amine

HRID 1442515ノート

反応式

HRID 1442515 の反応式
[CH:1]1([CH2:6][N:7]([CH2:31][CH3:32])[C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][C:9]=2[CH2:18][NH:19][C:20]2[N:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][S:29][CH3:30])=[CH:22][N:21]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Br[CH:36]([C:38]1[CH:43]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:41]=[C:40]([C:48]([F:51])([F:50])[F:49])[CH:39]=1)[CH3:37].O>O1CCCC1.CN(C)C=O>[F:45][C:44]([F:46])([F:47])[C:42]1[CH:43]=[C:38]([CH:36]([N:19]([CH2:18][C:9]2[CH:10]=[C:11]([C:14]([F:15])([F:16])[F:17])[CH:12]=[CH:13][C:8]=2[N:7]([CH2:6][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)[CH2:31][CH3:32])[C:20]2[N:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][S:29][CH3:30])=[CH:22][N:21]=2)[CH3:37])[CH:39]=[C:40]([C:48]([F:49])([F:50])[F:51])[CH:41]=1

参加物

7

反応物 4

HCID 962WaterHCID 24758Sodium hydrideHCID 129473971-(1-Bromoethyl)-3,5-bis(trifluoromethyl)benzeneHCID 68491507N-({2-[(cyclopentylmethyl)(ethyl)amino]-5-(trifluoromethyl)phenyl}methyl)-5-[2-(methylthio)ethoxy]pyrimidin-2-amine

生成物 1

HCID 25056258N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({2-[(cyclopentylmethyl)(ethyl)amino]-5-(trifluoromethyl)phenyl}methyl)-5-[2-(methylthio)ethoxy]pyrimidin-2-amine収率 91%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
50 °C

実験手順

To a stirred solution of N-({2-[(cyclopentylmethyl)(ethyl)amino]-5-(trifluoromethyl)phenyl}methyl)-5-[2-(methylthio)ethoxy]pyrimidin-2-amine (4.39 g, 9.37 mmol) in tetrahydrofuran (40 mL) under ice cooling was added sodium hydride (50% in oil, 1.80 g, 37.5 mmol), and the mixture was stirred at 50° C. for 1 hour. After cooling to −78° C., to the reaction mixture was added a solution of 1-bromo-1-[3,5-bis(trifluoromethyl)phenyl]ethane (6.02 g, 18.7 mmol) obtained in Step 2 in N,N-dimethylformamide (40 mL), and the mixture was stirred for 2.5 hours with warming to room temperature. The reaction mixture was added with water and extracted with ethyl acetate, the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=20:1) to obtain the target compound, N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({2-[(cyclopentylmethyl)(ethyl)amino]-5-(trifluoromethyl)phenyl}methyl)-5-[2-(methylthio)ethoxy]pyrimidin-2-amine (6.03 g, 91%), as a pale yellow oil.

後処理

  1. temperatureAfter cooling to −78° C., to the reaction mixture
  2. stirringthe mixture was stirred for 2.5 hours
  3. temperaturewith warming to room temperature
  4. extractionextracted with ethyl acetate
  5. washthe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customthe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=20:1)

出典と根拠

ORDレコード
ord-79c9ad82fa9241e3b971fe50ee91cca0
出典データセット
uspto-grants-2010_02
特許番号
US07659271B2

反応ノート

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