反应详情

To a solution of 1-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}cyclobutanol (4.05 g, 13.0 mmol) in dichloromethane (85 mL) at rt was added m-CPBA (55%, 4.08 g, 13.0 mmol). After 1 h, concentrated ammonium hydroxide (85 mL) was added, followed by TsCl (2.73 g, 14.3 mmol). The reaction was stirred rapidly for 2 d. More TsCl (0.25 g) was added and the mixture was stirred one day more. The layers were separated. Water was added to the aqueous layer, which was extracted twice with dichloromethane. The combined organic layers were washed with water and brine, dried over Na2SO4, filtered, and concentrated to a pale yellow foam. Acetonitrile was added to the foam, causing a solid to form. The solid was triturated with hot acetonitrile to yield an off white solid that was crystallized from acetonitrile/dichloromethane. Pale yellow crystals were isolated by filtration and dried under vacuum 80° C. to yield 1.81 g (43%) of 1-{[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}cyclobutanol, mp 174-175° C. 1H NMR (CDCl3, 300 MHz) δ 8.23 (dd, J=8.3, 1.4 Hz, 1H), 7.78 (dd, J=8.4, 1.4 Hz, 1H), 7.50 (ddd, J=8.4, 7.0, 1.4 Hz, 1H), 7.31 (ddd, J=8.4, 7.0, 1.4 Hz, 1H), 5.41 (br s, 2H), 4.893 (s, 2H), 4.886 (s, 2H), 3.64 (q, J=7.0 Hz, 2H), 3.50 (br s, 1H), 2.35-2.27 (m, 2H), 2.10-1.78 (m, 4H), 1.25 (t, J=7.0 Hz, 3H); MS (APCI) m/z 327 (M+H+); Anal. calcd for C18H22N4O2: C, 66.24; H, 6.79; N, 17.16. Found: C, 66.02; H, 6.87; N, 17.09.

1. stirringthe mixture was stirred one day more
2. customThe layers were separated
3. additionWater was added to the aqueous layer, which
4. extractionwas extracted twice with dichloromethane
5. washThe combined organic layers were washed with water and brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated to a pale yellow foam
9. additionAcetonitrile was added to the foam
10. customto form
11. customThe solid was triturated with hot acetonitrile
12. customto yield an off white solid
13. customthat was crystallized from acetonitrile/dichloromethane
14. customPale yellow crystals were isolated by filtration
15. customdried under vacuum 80° C.