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

Yield:-

Reaction Conditions:

with 2-methoxy-ethanol;sodium hydroxide at 125; for 1 h;

Steps:

64.2

Step 64.2: 4-Methyl-5-r2-(2,2,2-trifluoro-1 ,1-dimethyl-ethyl)-pyrimidin-4-yll-thiazol-2-ylamine; 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 ⁰C 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.

References:

WO2010/29082,2010,A1 Location in patent:Page/Page column 103-104