Triethylamine → tert-Butyl 3-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)azetidine-1-carboxylate

Participants

Reaction Steps

Zinc(II) chloride (1.0 M in Et2O; 4.83 mL, 4.83 mmol) was added to a solution of 2,4-dichloro-5-(trifluoromethyl)pyrimidine (0.769 g, 3.54 mmol) in DCE/t-BuOH (64 mL) at room temperature under nitrogen. After stirring for 10 minutes, tert-butyl 3-(4-aminophenyl)azetidine-1-carboxylate (A77) (0.800 g, 3.22 mmol) was added followed by Et3N (1.08 mL, 7.73 mmol). The resulting mixture was stirred at room temperature for 20 hours then the volatiles removed in vacuo. Water was added to the residue and the resulting suspension sonicated for 2 minutes. The suspension was filtered and the filter cake dried then adsorbed onto silica gel and purified using column chromatography (CombiFlash Rf, 40 g SiO2 cartridge, 10-40% EtOAc in cyclohexane) to give a white solid. The solid was suspended in MeOH (7 mL) and the resulting suspension sonicated for 30 seconds. The suspension was filtered and the filter cake washed with MeOH (3 mL), then dried to give the title compound A78 as a white solid (0.777 g, 56%); 1H NMR (300 MHz, d6-DMSO) δ 10.6 (s, 1H), 8.79 (s, 1H), 7.66 (d, J=8.4 Hz, 2H), 7.33 (d, J=8.4 Hz, 2H), 4.23 (t, J=7.6 Hz, 2H), 3.85-3.74 (m, 3H), 1.40 (s, 9H). LCMS-B: rt 8.810 min; m/z 429 [M+H]+.

Provenance & Evidence