Sodium → N-[imino(propylamino)methyl]-3-[2-(3-methoxypropoxy)-4'-(morpholin-4-ylcarbonyl) biphenyl-4-yl]-propanamide hydrochloride

Participants

Reaction Steps

Sodium (0.09 g, 3.9 mmol) was dissolved in ethanol (2 mL) at room temperature. Once all the sodium was dissolved, propylguanidine hydrochloride (0.54 g, 3.9 mmol) was added and the mixture was stirred for 1 hr. 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′-(morpholin-4-ylcarbonyl)biphenyl-4-yl]propanoate (0.28 g, 0.6 mmol) and DMF (2 mL) was added at room temperature. After completion of the reaction, the mixture was 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, 2 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 0.08 g (25%) of the desired product as a white solid: mp=79° C.; 1H NMR (400 MHZ, d6-DMSO) δ 12.02 (bs, 1H), 9.03 (bs, 1H), 8.69 (bs, 1H), 7.49 (m, 4H), 7.23 (d, 1H), 7.02 (s, 1H), 6.90 (d, 1H), 4.08 (t, 2H), 3.57 (m, 6H), 3.50 (m, 4H), 3.26 (t, 2H), 3.17 (s, 3H), 2.98 (t, 2H), 2.80 (t, 2H), 1.88 (m, 2H), 1.51 (q, 2H), 0.90 (t, 3H).

Provenance & Evidence