反应详情

Boron tribromide (7.4 mL, 1 M solution in dichloromethane, 7.4 mmol) was added to a solution of 4-chloro-2-(2-methoxy-phenyl)-quinazoline (0.200 g, 0.739 mmol) in dichloromethane (5 mL) at 0° C. After 24 hours the solution was poured into ice-water (200 mL) and extracted with dichloromethane (2×100 mL). The organic layers were combined, washed with brine (100 mL), dried (MgSO4) and concentrated to give a yellow solid that was used immediately without further purification. Half of the material (0.370 mmol) was dissolved in N,N-dimethylacetamide and 1-methylpiperidine-3-amine dihydrochloride (0.083 g, 0.444 mmol) was added. Triethylamine (258 μL, 1.850 mmol) was added and the reaction was stirred for 1 hour. The mixture was concentrated and purified by ion exchange chromatography on SCX-2 Isolute acidic resin (2 g), eluting with methanol and then 1 M ammonia in methanol. The basic fractions were combined and purified by silica column chromatography, eluting with 10% methanol in dichloromethane, to give the title compound as a yellow solid (0.103 g, 83%).

1. extractionextracted with dichloromethane (2×100 mL)
2. washwashed with brine (100 mL)
3. dry with materialdried (MgSO4)
4. concentrationconcentrated
5. customto give a yellow solid that
6. customwas used immediately without further purification
7. concentrationThe mixture was concentrated
8. custompurified by ion exchange chromatography on SCX-2 Isolute acidic resin (2 g)
9. washeluting with methanol
10. custompurified by silica column chromatography
11. washeluting with 10% methanol in dichloromethane