反应详情

N-[2-(2-Diethylamino-ethylamino)-5-nitro-phenyl]-2-(4-ethoxy-phenyl)-acetamide 6a (295 mg, 0.712 mmol), Phosphorous pentachloride (148.3 mg, 0.712 mmol) were dissolved in anhydrous chloroform (10 mL) in a small, argon purged flask fitted with a condenser and magnetic stirbar. The solution was heated to reflux in an oil bath for 4 hours and cooled to room temperature overnight. The mixture was diluted with H2O and chloroform and 2M ammonium hydroxide solution added to adjust pH to 9-10. The mixture was transferred to a separatory funnel and the organic layer collected. The aqueous layer was further extracted with chloroform and the combined organic layers were washed with brine, dried over magnesium sulphate, filtered and concentrated to afford crude. The product was purified using dry silica gel column chromatography eluting with 25 mL portions of solvent system (2.5% 2M NH3 in methanol/95% dichloromethane) to afford a yellow residue. Recrystallization from diethyl ether/hexanes at 0° C. yielded a pale yellow solid 7a {2-[2-(4-Ethoxy-benzyl)-5-nitro-benzoimidazol-1-yl]-ethyl}-diethyl-amine. Yield: 177 mg (62.7%). 1H NMR (DMSO) : 0.71 (t, 6H, J=7.0), 1.29 (t, 3H, J=7.0), 2.37 (q, 4H, J=7.1), 2.50 (m, 2H), 3.98 (q, 2H, J=6.9), 4.25 (m, 2H), 4.32 (s, 2H), 6.87 (d, 2H, J=8.4), 7.19 (d, 2H, J=8.4), 7.71 (d, 1H, J=8.9), 8.14 (dd, 2H, J=8.9, 2.1), 8.45 (d, 1H, J=2.1); MS (ESI): 397 (MH+, 100%)

1. customfitted with a condenser
2. temperatureThe solution was heated
3. temperatureto reflux in an oil bath for 4 hours
4. additionadded
5. customThe mixture was transferred to a separatory funnel
6. customthe organic layer collected
7. extractionThe aqueous layer was further extracted with chloroform
8. washthe combined organic layers were washed with brine
9. dry with materialdried over magnesium sulphate
10. filtrationfiltered
11. concentrationconcentrated
12. customto afford crude
13. customThe product was purified
14. washeluting with 25 mL portions of solvent system (2.5% 2M NH3 in methanol/95% dichloromethane)
15. customto afford a yellow residue
16. customRecrystallization from diethyl ether/hexanes at 0° C.