1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 3-(3-Chloro-phenyl)-5-[1-(4-methyl-5-thiophen-2-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-ethyl]-[1,2,4]oxadiazole

Participants

Reaction Conditions

Reaction Steps

DMF was added to a mixture of 2-(4-Methyl-5-thiophen-2-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-propionic acid (50 mg, 0.186 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (35.7 mg, 0.186 mmol), 1-hydroxybenzotriazole hydrate (HOBT) (28.5 mg, 0.186 mmol) and 3-chloro-N-hydroxy-benzamidine (29.3 mg, 0.172 mmol) at room temperature and stirred overnight. The reaction mixture was diluted lo with ethyl acetate (75 ml), washed with water 3 times, once with 1.0 M HCl (30 ml), saturated NaHCO3 (30 ml) and saturated brine (30 ml), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. DMF (1 ml) was added to the residue and the resulting solution was heated at 135° C. for 3 h to effect cyclization to oxadiazole. After cooling the reaction mixture was diluted with ethyl acetate (75 ml), washed with water 3 times, once with 1.0 M HCl (30 ml), saturated NaHCO3 (30 ml) and saturated brine (30 ml), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The title compound (46.5 mg, 66.9%) was purified by SPE chromatography on silica gel using 50 ml 40%, 150 ml 50% ethyl acetate in hexanes. 1H NMR (CDCl3), a (ppm): 8.03 (s, 1H), 7.92 (m, 1H), 7.47 (m, 4H), 7.18 (dd, 1H), 4.99 (q, 1H), 3.64 (s, 3H), 1.97 (d, 3H).

Provenance & Evidence