Dimethyl Sulfoxide → 4-(4-(1-(2-(Dimethylamino)ethyl)-4-(4-fluoro-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-7-(2,4-dimethoxybenzyl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one

Participants

Reaction Conditions

Reaction Steps

Combine 2-(4-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(piperidin-4-yl)-1H-imidazol-1-yl)-N,N-dimethylethanamine trihydrochloride (98.76 g, 1 eq), DMSO (395 mL) and 4-chloro-7-(2,4-dimethoxybenzyl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one (1.1 eq). Heat the resulting suspension to 60-65° C. then add TEA (6 eq). Stir for 6 hours. Add DMSO (395 mL) and water (150 mL) as a stream and stir the resulting suspension for 1 hour at 45-38° C. Filter the slurry and wash the solids with a mixture of DMSO (1 vol) and water (1 vol) two times. Further wash the solids with water (3×200 mL), methanol (3×200 mL) and heptane (3×200 mL). Dry the cake on the filter to afford the target compound (106.5 g, 79.75% yield) as a tan solid. 1H NMR (400 MHz, DMSO): 8.18 (s, 1H), 7.99-7.95 (m, 2H), 7.71 (s, 1H), 7.43-7.39 (m, 2H), 6.76 (d, J=7.1 Hz, 1H), 6.54 (d, J=2 Hz 1H), 6.38-6.35 (m, 1H), 4.67 (s, 2H), 4.49 (d, J=13.1 Hz, 2H), 4.03 (t, J=6.52, 2H), 3.89 (s, 2H), 3.78 (s, 3H), 3.69 (s, 3H), 3.15-3.09 (m, 3H), 2.57 (t, J=6.6 Hz, 2H), 2.18 (s, 6H), 1.89-1.74 (m, 4H).

Provenance & Evidence