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

HRID 1516238노트

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HRID 1516238 반응식
[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

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 80192-Methoxyethanol용매

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온도
125 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-83e4d2fb20f348d7a427262aeccf620a
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08227462B2

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