2-(4-(trifluoromethyl)phenyl)imidazo[1,2-a]pyrimidine synthesis

Yield:1449488-26-9 66%

Reaction Conditions:

with sodium hydrogencarbonate in ethanol; for 8 h;Reflux;

Steps:

3

General procedure: To a solution of 2-aminoheteroarene (10mmol) in ethanol (50mL), phenacyl bromide (10mmol) and NaHCO₃ (30mmol) were added at rt and the reaction mixture was refluxed for 8h. On removal of solvent, the residue was dissolved with ethyl acetate (100mL) and washed with water (50mL), brine (50mL), and dried over sodium sulfate. The solvent was evaporated to give crude product, which was purified by combiflash chromatography (1-20% EtOAc/PE) to give the desired product 2-(4-(trifluoromethyl)phenyl)imidazo[1,2-a]pyrimidine (4b)
Isolated yield 66%; R_f (1:9 MeOH/chloroform) 0.53; off white solid: mp 233-235 °C; ¹H NMR (300 MHz, CDCl₃) δ (ppm): 7.46 (dd, J=4.2, 6.6 Hz, 1H), 7.94 (d, J=8.1 Hz, 2H), 8.24 (d, J=8.1 Hz, 2H), 8.78 (s, 1H), 8.88 (dd, J=1.6, 4.2 Hz, 1H), 9.22 (dd, J=1.8 Hz, 4.2 Hz, 1H); ¹³C NMR (75 MHz, CDCl₃) δ (ppm): 111.1, 113.4, 126.7 (q), 127.3 (*2C), 132.7, 137.1, 137.9 (*2C), 145.9, 156.6; HRMS (ESI): m/z [M+H]⁺ calcd for C₁₃H₉F₃N₃: 264.0743, found 264.0746; HPLC: 96.3%.

References:

Patil, Shashikant M.;Kulkarni, Sarang;Mascarenhas, Malcolm;Sharma, Rajiv;Roopan, S. Mohana;Roychowdhury, Abhijit [Tetrahedron,2013,vol. 69,# 38,p. 8255 - 8262]