Cesium carbonate → N-(2-chloro-5-pyrimidinyl)-4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-amine

Participants

Reaction Conditions

Reaction Steps

A mixture of 0.28 g (0.71 mmol) of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole, 0.076 g (0.56 mmol) of the above amine, 0.026 g (0.04 mmol) of BINAP, 0.01 g (0.04 mmol) of Pd(OAc)2, and 0.266 g (0.82 mmol) of Cs2CO3 in 1,4-dioxane (4 mL) was heated at 100° C. for 3 hrs under nitrogen. The mixture was cooled to room temperature, sat. NaHCO3 solution was added, and the resulting mixture was extracted with EtOAc (×4). The organic layer was washed with brine, dried (Na2SO4), and concentrated. Chromatography on silica, eluting with CH2Cl2/EtOAc (6:1), gave 0.10 g (36% yield) of N-(2-chloro-5-pyrimidinyl)-4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-amine, as a white powder: mp 295° C. (decomp.); 1H NMR (DMSO-d6) δ 10.43 (s, 1H), 9.08 (s, 2H), 8.09-7.69 (m, 2H), 7.42 (t, J=8.0 Hz, 1H), 6.98 (d, J=7.6 Hz, 1H), 3.98 (s, 3H), 3.83 (s, 4H), 3.75-3.73 (m, 4H); Anal. Calcd. for C20H18ClF2N9O2: C, 49.0; H, 3.7; N, 25.7. Found: C, 49.2; H, 3.9; N, 25.45%.

Provenance & Evidence