Ethanol → Methyl 3-(2-(3-(benzyloxy)-5-(2-chlorophenoxy)pyridin-2-ylamino)thiazol-4-yl)propanoate

Participants

Reaction Steps

A mixture of 1-(3-(benzyloxy)-5-(2-chlorophenoxy)pyridin-2-yl)thiourea (0.471 g, 1.11 mmol), methyl 5-bromo-4-oxopentanoate (0.279 g, 1.33 mmol), triethylamine (0.271 ml, 1.94 mmol), and ethanol (10 mL) was heated at reflux for 2 hours, cooled, partitioned between ethyl acetate and 2N NaOH, washed with water and brine, dried, and concentrated. The residue was purified by MPLC (Biotage) eluting with 3:1 hexane:ethyl acetate to afford methyl 3-(2-(3-(benzyloxy)-5-(2-chlorophenoxy)pyridin-2-ylamino)thiazol-4-yl)propanoate (0.392 g, 71.2% yield) as a white viscous oil/wax. The compound (70 mg) was dissolved in ether (2 mL) and 1N HCl in ether (0.5 mL) was added. The mixture was stirred 5 minutes, and hexanes (5 mL) were added. The mixture was decanted, and a mixture of hexanes:ether (2:1, 3 mL) was added three times with three decantations. The solid material was dried to afford methyl 3-(2-(3-(benzyloxy)-5-(2-chlorophenoxy)pyridin-2-ylamino)thiazol-4-yl)propanoate hydrochloride (0.058 g, 9.81% yield) as a white solid. 1H NMR (DMSO-d6) δ 2.73 (t, 2H), 3.61 (s, 3H), 2.91 (t, 2H), 5.32 (s, 2H), 6.82 (s, 1H), 6.99 (d, 1H), 7.21 (t, 1H), 7.31-7.43 (m, 4H), 7.47 (d, 1H), 7.55-7.66 (m, 5H).

Provenance & Evidence