反应详情

{2-[2-(4-Ethoxy-benzyl)-5-nitro-benzoimidazol-1-yl]-ethyl}-diethyl-amine 7a (108 mg, 0.273 mmol) was reduced to the amine 8a as outlined above and the resulting ethanolic solution charged to a small, argon purged flask fitted with a magnetic stirbar. Thiophene-3-carboximidothioic acid benzyl ester hydrobromide 9f (182 mg, 0.575 mmol) is added to the flask and the reaction was stirred under Ar at ambient temperature for 108 hours. The solvent was evaporated and the residue partitioned between H2O and ethyl acetate and 3M sodium hydroxide solution added to adjust pH to 10. The mixture was transferred to a separatory funnel and the organic layer collected. The aqueous layer was further extracted with ethyl acetate and the combined organic layers were washed with brine (twice), dried over magnesium sulphate, filtered and concentrated to afford crude. The product was purified using silica gel dry column chromatography eluting with 5% 2M NH3 in methanol/95% dichloromethane then purified using a second silica gel column eluting with 60% methanol/40% dichloromethane to afford a pale yellow solid 16 N-(1-(2-(diethylamino)ethyl)-2-(4-ethoxybenzyl)-1H-benzo[d]imidazol-5-yl)thiophene-3-carboximidamide. Yield: 40 mg (30.8%) 1H NMR (DMSO) δ; 0.83 (t, 6H, J=7.0), 1.30 (t, 3H, J=6.9), 2.38-2.50 (2×m, 6H), 3.97 (q, 2H, J=7.0), 4.10 (t, 2H, J=6.5), 4.22 (s, 2H), 6.12 (br, 2H), 6.73 (d, 1H, J=8.3), 6.86 (d, 2H, J=8.4), 6.97 (d, 1H, J=1.8), 7.19 (d, 2H, J=8.6), 7.34 (d, 1H, J=8.4), 7.53-7.55 (m, 1H), 7.61-7.66 (m, 1H), 8.13 (d, 1H, J=3.0). MS (ESI): 476 (MH+, 25%), 377 (100%).

1. additioncharged to a small, argon purged flask
2. customfitted with a magnetic stirbar
3. customThe solvent was evaporated
4. customthe residue partitioned between H2O and ethyl acetate and 3M sodium hydroxide solution
5. additionadded
6. customThe mixture was transferred to a separatory funnel
7. customthe organic layer collected
8. extractionThe aqueous layer was further extracted with ethyl acetate
9. washthe combined organic layers were washed with brine (twice),
10. dry with materialdried over magnesium sulphate
11. filtrationfiltered
12. concentrationconcentrated
13. customto afford crude
14. customThe product was purified
15. customdry column chromatography
16. washeluting with 5% 2M NH3 in methanol/95% dichloromethane
17. customthen purified
18. washeluting with 60% methanol/40% dichloromethane