反应详情

Similar to Example 57, a mixture of 1-[4-chloro-6-(4-morpholinyl)-2-pyrimidinyl]-2-(difluoromethyl)-1H-benzimidazole (200 mg, 0.547 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyrimidinylamine (302 mg, 1.38 mmol), PdCl2 (dppf) (45 mg, 0.0551 mmol) and aq. K2CO3 (2M, 4 mL) in 1,4-dioxane (20 mL) was refluxed under nitrogen for 24 hrs. The mixture was cooled to room temperature, diluted with H2O, extracted with CH2Cl2 (4×), and the combined organic extracts were dried (Na2SO4), and the solvents removed under vacuum. Chromatography on alumina, eluting with CH2Cl2/EtOAc (100:0 to 80:20) to CH2Cl2/MeOH (100:0 to 98.5:1.5), followed by recrystallization from CH2Cl2/MeOH/i-Pr2O gave 2-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-4,5′-bipyrimidine-2′-amine (157 mg, 66% yield): mp 281-285° C.; 1H NMR (DMSO-d6) δ 9.09 (s, 2H), 8.35 (d, J=8.2 Hz, 1H), 7.86 (d, J=8.0 Hz, 1H), 7.79 (t, Jjw=52.8 Hz, 1H), 7.52 (t, J=7.5 Hz, 1H), 7.43 (t, J=7.3 Hz, 1H), 7.32 (s, 1H), 7.24 (s, 2H), 3.82 (m, 4H), 3.77 (m, 4H).

1. temperaturewas refluxed under nitrogen for 24 hrs
2. extractionextracted with CH2Cl2 (4×)
3. dry with materialthe combined organic extracts were dried (Na2SO4)
4. customthe solvents removed under vacuum
5. washChromatography on alumina, eluting with CH2Cl2/EtOAc (100:0 to 80:20) to CH2Cl2/MeOH (100:0 to 98.5:1.5)
6. customfollowed by recrystallization from CH2Cl2/MeOH/i-Pr2O