Diethyl Ether → HCID 86675723, compound

Participants

Reaction Conditions

Reaction Steps

2,4-Dichloro-5-(trifluoromethyl)pyrimidine (0.551 g, 2.54 mmol) was stirred in a 1:1 t-BuOH:1,2-dichloroethane mixture (30 mL) at 0° C. A 1.0 M ZnCl2 solution in diethyl ether (2.903 mL, 2.903 mmol) was added cautiously over 10 minutes, after addition the reaction was left stirring at 0° C. for 30 minutes. A solution of tert-butyl (1-(4-aminophenyl)piperidin-4-yl)carbamate (I75) (0.705 g, 2.42 mmol) in 1:1 t-BuOH:1,2-dichloroethane (15 mL) was added drop-wise over 15 minutes at 0° C., a solution of NEt3 (0.405 mL, 2.903 mmol) in 1:1 t-BuOH:1,2-dichloroethane (15 mL) was added drop-wise over 15 minutes and the reaction was allowed to warm to room temperature and was stirred for 18 hours. The organic solvents were evaporated in vacuo and the crude oily solid was suspended in water (200 mL), the suspension was sonicated for 30 minutes and the product was separated by filtration, the solid was washed with water (10×20 mL) and dried under a high vacuum. The material was further purified by silica gel chromatography using a gradient of 0-50% ethyl acetate in petroleum benzine 40-60° C. to give the title compound (I76) (0.730 g, 64%) as a yellow solid; 1H NMR (400 MHz, d6-DMSO) δ 10.41 (s, 1H), 8.71 (s, 1H), 7.46 (d, J=7.7 Hz, 2H), 6.92 (d, J=8.9 Hz, 2H), 6.84 (d, J=7.1 Hz, 1H), 3.60 (d, J=12.4 Hz, 2H), 2.69 (t, J=10.9 Hz, 2H), 1.78 (d, J=10.9 Hz, 2H), 1.54-1.34 (m, 11H). LCMS Method C: rt 6.36 min; m/z 474.1 [M+H]+.

Provenance & Evidence