Potassium Carbonate → tert-butyl 1-[4-chloro-6-(4-morpholinyl)-2-pyrimidinyl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazol-6-ylcarbamate

Participants

Reaction Conditions

Reaction Steps

A mixture of tert-butyl 2-(difluoromethyl)-4-methoxy-1H-benzimidazol-6-yl-carbamate (Example 64) (3.13 g, 10 mmol), 4-(2,6-dichloro-4-pyrimidinyl)morpholine (2.64 g, 11 mmol), and powdered K2CO3 (5 g, 40 mmol) in 30 mL DMF was heated at 100° C. for 8 hrs. The mixture was cooled and diluted with water to give a precipitate which was collected and dried. Chromatography on silica eluting with CH2Cl2/EtOAc (19:1) gave tert-butyl 1-[4-chloro-6-(4-morpholinyl)-2-pyrimidinyl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazol-6-ylcarbamate (2.49 g, 44% yield): mp (i-Pr2O) 233-236° C.; 1H NMR (CDCl3) δ 8.30 (s, 1H), 7.57 (t, JHF=53.8 Hz, 1H), 6.64 (m, 1H), 6.63 (d, J=1.8 Hz, 1H), 6.43 (s, 1H), 4.01 (s, 3H), 3.88-3.85 (m, 4H), 3.82-3.77 (m, 4H), 1.52 (s, 9H); Anal. Calcd. for C22H25ClF2N6O4: C, 51.7; H, 4.9; N, 16.45. Found: C, 52.0; H, 4.9; N, 16.6%.

Provenance & Evidence