反应详情

To a suspension of cis-N2-(4-amino-cyclohexyl)-N4,N4-dimethyl-quinazoline-2,4-diamine obtained in step C of example 9 (300 mg, 1.05 mmol) in CH2Cl2 (3 mL) were added (4-bromo-2-trifluoromethoxy-phenyl)-acetaldehyde (357 mg, 1.26 mmol), AcOH (76 mg, 1.26 mmol), and NaBH(OAc)3 (334 mg, 1.57 mmol). The reaction mixture was stirred at ambient temperature for 4.5 hr. The reaction was quenched with saturated aqueous NaHCO3 The aqueous layer was extracted with CHCl3 (three times). The combined organic layer was dried over MgSO4, filtered, concentrated, and purified by flash chromatography (NH-silica gel, 50% EtOAc in hexane) to give a pale yellow solid. To a solution of above solid in EtOAc (0.8 mL) was added 4 M hydrogen chloride in EtOAc (0.25 mL). The mixture was stirred at ambient temperature for 30 min and concentrated. A solution of the residue in Et2O (2 mL) was stirred at ambient tempareture for 30 min. The precipitate was collected by filtration, washed with Et2O, and dried under reduced pressure to give cis-N2-{4-[2-(4-bromo-2-trifluoromethoxy-phenyl)-ethylamino]-cyclohexyl}-N4,N4-dimethyl-quinazoline-2,4-diamine dihydrochloride (161 mg, 25%) as a white solid.

1. customThe reaction was quenched with saturated aqueous NaHCO3 The aqueous layer
2. extractionwas extracted with CHCl3 (three times)
3. dry with materialThe combined organic layer was dried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated
6. custompurified by flash chromatography (NH-silica gel, 50% EtOAc in hexane)
7. customto give a pale yellow solid
8. stirringThe mixture was stirred at ambient temperature for 30 min
9. concentrationconcentrated
10. stirringA solution of the residue in Et2O (2 mL) was stirred at ambient tempareture for 30 min
11. filtrationThe precipitate was collected by filtration
12. washwashed with Et2O
13. customdried under reduced pressure