Water → 4-Methyl-5-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrimidin-4-yl)thiazol-2-amine

HRID 2370391ノート

反応式

HRID 2370391 の反応式
[OH-].[Na+].CN(C)/[CH:5]=[CH:6]/[C:7]([C:9]1[S:13][C:12]([N:14]=CN(C)C)=[N:11][C:10]=1[CH3:19])=O.Cl.[F:22][C:23]([F:31])([F:30])[C:24]([CH3:29])([CH3:28])[C:25]([NH2:27])=[NH:26].O>COCCO>[CH3:19][C:10]1[N:11]=[C:12]([NH2:14])[S:13][C:9]=1[C:7]1[CH:6]=[CH:5][N:27]=[C:25]([C:24]([CH3:29])([CH3:28])[C:23]([F:31])([F:30])[F:22])[N:26]=1

参加物

6

反応物 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 67218484N'-[5-((E)-3-dimethylamino-acryloyl)-4-methyl-thiazol-2-yl]-N,N-dimethylformamidineHCID 86641156HCID 86641156、化合物

生成物 1

HCID 592937334-Methyl-5-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrimidin-4-yl)thiazol-2-amine

試薬・触媒・溶媒 1

HCID 80192-Methoxyethanol溶媒

反応条件

温度
125 °C

実験手順

Powdered sodium hydroxide (0.42 g) is added to a solution of N′-[5-((E)-3-dimethylamino-acryloyl)-4-methyl-thiazol-2-yl]-N,N-dimethyl-formamidine (0.93 g, prepared as described by S. Wang et al J. Med. Chem. 2004, 47, 1662-1675.) and 3,3,3-trifluoro-2,2-dimethyl-propionamidine hydrochloride (0.54 g) in 2-methoxyethanol (7 ml) and the mixture is heated at 125° C. for 1 hour with stirring. The reaction mixture is cooled, water is added, and the aqueous layer is extracted 4-times with 10% methanol in dichloromethane. The combined organic layers are purified by reversed phase chromatography and sodium bicarbonate is added to the fractions containing the title compound to give a white precipitate, which is collected by filtration. HPLC/MS: retention time 1.47 minutes, M+H 303.1.

後処理

  1. temperatureThe reaction mixture is cooled
  2. extractionthe aqueous layer is extracted 4-times with 10% methanol in dichloromethane
  3. customThe combined organic layers are purified by reversed phase chromatography and sodium bicarbonate
  4. additionis added to the fractions
  5. additioncontaining the title compound
  6. customto give a white precipitate, which
  7. filtrationis collected by filtration

出典と根拠

ORDレコード
ord-370c99825c764a82b35c8986b650831d
出典データセット
uspto-grants-2014_04
特許番号
US08710085B2

反応ノート

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