Ammonia → 4-Chloro-5-(trifluoromethyl)pyrimidin-2-amine
Reaction equation
[NH3:1].Cl[C:3]1[N:8]=[C:7]([Cl:9])[C:6]([C:10]([F:13])([F:12])[F:11])=[CH:5][N:4]=1>CO>[Cl:9][C:7]1[C:6]([C:10]([F:13])([F:12])[F:11])=[CH:5][N:4]=[C:3]([NH2:1])[N:8]=1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
Ammonia in methanol (7 N solution, 15 mL) was added dropwise to stirred neat 2,4-dichloro-5-(trifluoromethyl)pyrimidine 131 (5.0 g, 23.04 mmol) under argon, and the resulting mixture was stirred at RT for 2 h. The reaction mixture was quenched with water and then extracted with ethyl acetate (2×200 mL). The combined organic layers were washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash chromatography on silica gel (0-20% ethyl acetate-hexanes) to afford the product 4-chloro-5-(trifluoromethyl)pyrimidin-2-amine 132. The regio-isomer 2-chloro-5-(trifluoromethyl)pyrimidin-4-amine 133 can also be isolated.