Water → N-(4-((4-Aminopyrimidin-2-yloxy)methyl)benzyl)-2,2,2-trifluoroacetamide

HRID 1516779

反応式

HRID 1516779 の反応式
[F:1][C:2]([F:16])([F:15])[C:3]([NH:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][OH:14])=[CH:9][CH:8]=1)=[O:4].[H-].[Na+].Cl[C:20]1[N:25]=[C:24]([NH2:26])[CH:23]=[CH:22][N:21]=1.O>CC(N(C)C)=O>[NH2:26][C:24]1[CH:23]=[CH:22][N:21]=[C:20]([O:14][CH2:13][C:10]2[CH:11]=[CH:12][C:7]([CH2:6][NH:5][C:3](=[O:4])[C:2]([F:15])([F:16])[F:1])=[CH:8][CH:9]=2)[N:25]=1

参加物

6

反応物 4

HCID 962WaterHCID 24758Sodium hydrideHCID 3457522-Chloro-4-aminopyrimidineHCID 158522092,2,2-Trifluoro-N-{[4-(hydroxymethyl)phenyl]methyl}acetamide

生成物 1

HCID 86657016N-(4-((4-Aminopyrimidin-2-yloxy)methyl)benzyl)-2,2,2-trifluoroacetamide

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

反応条件

温度
90 °C

実験手順

760 mg (3.25 mmol) 2,2,2-Trifluoro-N-(4-hydroxymethyl-benzyl)-acetamide is dissolved in 3 mL dry dimethylacetamide under argon atmosphere, and 273 mg (8.15 mmol) NaH is added over 5 min. 211 mg (1.63 mmol) 2-Chloropyrimidin-4-amine is then added and the solution stirred at 90° C. over night. 1 mL Water is added carefully to quench all excess NaH, and the mixture poured into 50 ml of 0.5 N HCl. The crude product is extracted with ethyl acetate, the combined organic phases washed with brine and dried over MgSO4. After evaporation of the solvent, the product is purified by flash column chromatography (gradient ethyl acetate:cyclohexane from 1:1 to 3:1). Yield: 350 mg (52%). ESI-MS m/z 327 [M+H]+.

後処理

  1. customto quench all excess NaH
  2. additionthe mixture poured into 50 ml of 0.5 N HCl
  3. extractionThe crude product is extracted with ethyl acetate
  4. washthe combined organic phases washed with brine
  5. dry with materialdried over MgSO4
  6. customAfter evaporation of the solvent
  7. customthe product is purified by flash column chromatography (gradient ethyl acetate:cyclohexane from 1:1 to 3:1)

出典と根拠

ORDレコード
ord-b5beb94f72b34ae3b4a7a8f1a8096989
出典データセット
uspto-grants-2012_07
特許番号
US08227602B2

関連ノート

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