反应详情

A mixture of 2-(difluoromethyl)-4-methoxy-1-{4-(4-morpholinyl)-6-[4-(vinylsulfonyl)-1-piperazinyl]-1,3,5-triazin-2-yl}-1H-benzimidazole (Example 3) (150 mg, 0.280 mmol) and piperidine (0.14 mL, 1.42 mmol) in THF (20 mL) was stirred at room temperature for 4 hrs. 1,4-Dioxane (20 mL) was added and the mixture was refluxed for 18 hrs. After cooled to room temperature, the solvents were removed under vacuum. The residue was partitioned between CH2Cl2 and H2O. The layers were separated and the aqueous phase extracted with CH2Cl2 (1×). The combined organic extracts were dried (Na2SO4) and the solvent removed under vacuum. Chromatography on silica, eluting with CH2Cl2/MeOH (100:0 to 98:2) gave 2-(difluoromethyl)-4-methoxy-1-[4-(4-morpholinyl)-6-(4-{[2-(1-piperidinyl)ethyl]sulfonyl}-1-piperazinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (147 mg, 84%).

1. temperaturethe mixture was refluxed for 18 hrs
2. temperatureAfter cooled to room temperature
3. customthe solvents were removed under vacuum
4. customThe residue was partitioned between CH2Cl2 and H2O
5. customThe layers were separated
6. extractionthe aqueous phase extracted with CH2Cl2 (1×)
7. dry with materialThe combined organic extracts were dried (Na2SO4)
8. customthe solvent removed under vacuum
9. washChromatography on silica, eluting with CH2Cl2/MeOH (100:0 to 98:2)