反应详情

Sodium (0.15 g, 6.5 mmol) was dissolved in ethanol (3.5 mL) at room temperature. Once all the sodium was dissolved, propylguanidine hydrochloride (0.65 g, 6.5 mmol) was added and the mixture was stirred for 1 h. A white precipitate formed and was filtered off. The filtrate was evaporated under reduced pressure and a solution of ethyl 3-{2-(3-methoxypropoxy)-4′-[(4-methylpiperazin-1-yl)carbonyl]biphenyl-4-yl}-3-methylbutanoate (0.51 g, 1.0 mmol) and DMF (3.5 mL) was added at room temperature. The mixture was stirred at 50° C. until reaction was completed. The mixture was then poured into dichloromethane/brine (50/50). The aqueous layer was extracted three times with dichloromethane. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The residue was then dissolved in ethanol and HCl in diethyl ether (1N, 4 mL) was added. The mixture was evaporated and the residue was purified on reverse phase (C18) flash chromatography (H2O, HCl N/1000, acetonitrile, 100/0 to 80/20) to afford 0.20 g (35%) of the desired product as a white solid: mp=99° C.; 1H NMR (400 MHZ, d6-DMSO) δ 12.22 (bs, 1H), 11.15 (bs, 1H), 9.02 (t, 1H), 8.69 (bs, 1H), 7.58 (m, 4H), 7.30 (d, 1H), 7.15 (s, 1H), 7.09 (d, 1H), 4.08 (t, 2H), 3.38 (t, 2H), 3.21 (m, 10H), 3.18 (s, 3H), 2.81 (s, 2H), 2.73 (s, 3H), 1.86 (m, 2H), 1.49 (m, 2H), 1.41 (s, 6H), 0.87 (t, 3H).

1. customA white precipitate formed
2. filtrationwas filtered off
3. customThe filtrate was evaporated under reduced pressure
4. stirringThe mixture was stirred at 50° C. until reaction
5. extractionThe aqueous layer was extracted three times with dichloromethane
6. washThe combined organic layers were washed with brine
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationfiltered
9. customevaporated under reduced pressure
10. dissolutionThe residue was then dissolved in ethanol
11. additionHCl in diethyl ether (1N, 4 mL) was added
12. customThe mixture was evaporated
13. customthe residue was purified on reverse phase (C18) flash chromatography (H2O, HCl N/1000, acetonitrile, 100/0 to 80/20)