Potassium Carbonate → tert-Butyl (4-{4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(morpholin-4-yl)-1,3,5-triazin-2-yl}phenyl)carbamate

Participants

Reaction Steps

A mixture of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole (Example 2), 4-[(tert-butoxycarbonyl)amino]phenylboronic acid (90 mg, 0.380 mmol), PdCl2(dppf) (10.3 mg, 0.0126 mmol) and aq. K2CO3 (2M, 2 mL) in 1,4-dioxane (10 mL) was refluxed under nitrogen for 1 hr. The mixture was cooled to room temperature and diluted with H2O, and the aqueous phase was extracted with CH2Cl2 (3×). The combined organic extracts were dried (Na2SO4) and the solvent was removed under vacuum. Chromatography on alumina, eluting with CH2Cl2, followed by recrystallization from CH2Cl2/MeOH/hexanes gave tert-butyl 4-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]phenylcarbamate (99 mg, 71%): mp (CH2Cl2/MeOH/hexanes) 188-190° C.; 1H NMR (CDCl3) δ 8.41 (d, J=8.8 Hz, 2H), 8.08 (dd, J=8.4, 0.6 Hz, 1H), 7.62 (t, JHF=53.4 Hz, 1H), 7.52 (d, J=8.8 Hz, 2H), 7.41 (t, J=8.2 Hz, 1H), 6.86 (d, J=7.7 Hz, 1H), 6.69 (s, 1H), 4.12 (m, 2H), 4.07 (s, 3H), 3.99 (m, 2H), 3.85 (m, 4H), 1.55 (s, 9H); Anal. Calcd. for C27H29F2N7O4: C, 58.6; H, 5.3; N, 17.2. Found: C, 58.5; H, 5.0; N, 17.7%.

Provenance & Evidence