反应详情

A solution of 10-methyl-8,9,10,11-tetrahydropyridazino[1′,6′:1,2]imidazo[4,5-c]quinoline (1.56 g, 6.55 mmol) in chloroform (50 mL) was chilled in a cold water bath and treated with 3-chloroperoxybenzoic acid (2.35 g, 8.18 mmol, 70%). After 30 min, the reaction mixture was treated with concentrated NH4OH (25 mL), stirred rapidly to homogenize, and then treated with p-toluenesulfonyl chloride (1.31 g, 6.88 mmol). After 20 min, the mixture was diluted with chloroform (25 mL) and water (25 mL) transferred to a separatory funnel and separated. The organic portion was washed with 10% Na2CO3 aqueous solution (25 mL), water (25 mL) and brine (25 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to yield a tan solid. The solid was purified by column chromatography (50 g silica gel eluted with 95:5 chloroform:methanol) to give an off white solid. The solid then was dissolved in 85:15 chloroform:methanol, stirred with activated carbon (0.100 g, Darco G-60), filtered through layer of CELITE filter agent, and concentrated under reduced pressure to yield 0.079 g of 10-methyl-8,9,10,11-tetrahydropyridazino[1′,6′:1,2]imidazo[4,5-c]quinolin-6-amine as an off white solid, mp 241-243° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.52 (dd, J=8.1, 1.3 Hz, 1H), 7.53 (dd, J=8.3, 1.5 Hz, 1H), 7.39-7.34 (m, 1H), 7.21-7.15 (m, 1H), 6.68 (d, J=10.5 Hz, 1H), 6.46 (s, 2H), 3.44-3.31 (m, 1H), 3.14-3.08 (m, 2H), 2.14-2.07 (m, 1H), 1.79-1.66 (m, 1 H), 1.27 (d, J=6.6 Hz, 3H); 13C NMR (75 MHz, DMSO-d6) δ 151.4, 144.3, 143.9, 129.9, 126.1, 125.2, 123.3, 121.1, 120.2, 114.8, 50.4, 27.3, 22.2, 18.2; MS (APCI) m/z 254 (M+H)+.

1. stirringto homogenize
2. waitAfter 20 min
3. customtransferred to a separatory funnel
4. customseparated
5. washThe organic portion was washed with 10% Na2CO3 aqueous solution (25 mL), water (25 mL) and brine (25 mL)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customto yield a tan solid
10. customThe solid was purified by column chromatography (50 g silica gel eluted with 95:5 chloroform:methanol)
11. customto give an off white solid
12. filtrationfiltered through layer of CELITE filter agent
13. concentrationconcentrated under reduced pressure