反应详情

To a solution of [7-methoxy-8-hydroxy-1,3,4,5-tetrahydro-benzo[c]azepin-2-yl]-pyridin-4-yl amine hydrochloride (500 mg) in chloroform (10 mL) was added 1,2,3,4-tetrahydroisoquinoline-2-yl carbonyl chloride (362 mg) followed by triethylamine (0.75 mL). The reaction mixture was heated under reflux for 3 hrs, cooled to ambient temperature, diluted with dichloromethane (200 mL), and the mixture was washed with saturated sodium bicarbonate solution. The organic phase was separated, dried under anhydrous magnesium sulfate, filtered, and the filtrate was concentrated in vacuo. The residue was flash chromatographed over silica gel, eluting with chloroform:methanol (9:1). The appropriate fractions were collected and evaporated. The residue was dissolved in methanol and conc hydrochloric acid was added. The precipitate was collected and crystallized from ethyl acetate-petroleum ether to give 230 mg of product, mp >100° C. (dec).

1. temperatureThe reaction mixture was heated
2. temperatureunder reflux for 3 hrs
3. washthe mixture was washed with saturated sodium bicarbonate solution
4. customThe organic phase was separated
5. customdried under anhydrous magnesium sulfate
6. filtrationfiltered
7. concentrationthe filtrate was concentrated in vacuo
8. customchromatographed over silica gel
9. washeluting with chloroform:methanol (9:1)
10. customThe appropriate fractions were collected
11. customevaporated
12. dissolutionThe residue was dissolved in methanol
13. additionconc hydrochloric acid was added
14. customThe precipitate was collected
15. customcrystallized from ethyl acetate-petroleum ether