Tributyltin Chloride → 3-[3-(Thien-2-yl)-[1,2,4]thiadiazol-5-yl]-7-trifluoromethylimidazo[1,2-alpha]pyrimidine

Participants

Reaction Conditions

Reaction Steps

A solution of iPrMgCl (2.0M in THF, 1.13 ml, 2.26 mmol) was added dropwise to a stirred suspension of 3-bromo-7-trifluoromethylimidazo[1,2-α]pyrimidine (547 mg, 2.06 mmol) in THF (20 ml) at −78° C. under N2. The resulting solution was stirred at −78° C. for 15 min and then tributyltin chloride (670 μl, 2.47 mmol) was added. The reaction was warmed to 0° C. and stirred for 1 h. 5-Chloro-3-(thien-2-yl)-[1,2,4]thiadiazole (500 mg, 2.47 mmol) and tetrakis(triphenylphosphine)palladium(0) (237 mg, 0.21 mmol) were added and the reaction heated at reflux for 1 h. Copper(I) iodide (50 mg, 0.26 mmol) was added and heating continued for a further 1.5 h. The mixture was concentrated under reduced pressure while dry loading onto silica. The resulting crude residue was purified by column chromatography on silica, using 50% EtOAc in hexane as the eluent, and subsequent recystallisation from dichloromethane/isohexanes gave 3-[3-(thien-2-yl)-[1,2,4]thiadiazol-5-yl]-7-trifluoromethylimidazo[1,2-α]pyrimidine (188 mg, 26%): δH (400 MHz, d6-DMSO) 7.30 (1H, t, J 3.7), 7.83-7.90 (2H, m), 8.11 (1H, dd, J 3.7 and 1.1), 9.14 (1H, s), 10.20 (1H, d, J 7.1); m/z (ES+) 353 (M+).

Provenance & Evidence