(+-)-Mercaptosuccinic acid → [3-(2-Carbamoyl-ethyl)-4-oxo-2-(5-phenylethynyl-thiophen-2-yl)-thiazolidin-5-yl]-acetic acid

Participants

Reaction Steps

A mixture of β-alanine amide hydrochloride (3.11 g, 25 mmol), 5-(phenylethynyl)thiophene-2-carboxaldehyde (5.31 g, 25 mmol), mercaptosuccinic acid (11.26 g, 75 mmol) and diisopropylethylamine (3.6 g, 27.5 mmol) was stirred in acetonitrile (300 mL) at reflux for forty eight hours. The solvent was evaporated and the residue was shaken with 2 N HCl (500 mL) and ethyl acetate (3×200 mL) The ethyl acetate solution was washed with water then brine and dried (MgSO4) and evaporated. The product was purified on a 600 mL. silica dry column by elution with dichloromethane:acetic acid (99:1) followed by dichloromethane:methanol:acetic acid (95:5:1). The appropriate fractions were evaporated. The residue was washed with ether and dried to provide the title compound as a white solid: (2.44 g, 23.5%): m.p. 175-178. 1H-NMR (DMSO-d6) δ 12.6 (broad, 1H), 7.56-7.57 (d, 1H, J=2.4 Hz), 7.54-7.55 (d, 1H, J=3.6 Hz), 7.4-7.46 (m, 4H), 7.28-7.32 (m, 2H), 6.90(s, 1H), 6.15 (s, 0.5 H), 6.12-6.13 (d, 0.5H, J=1.6 Hz), 4.24-4.28 (m, 1H), 4.15-4.19 (dd, 0.5H, J=3.6 Hz), 2.97-3.09 (m, 1H), 2.64-2.74 (m, 1H), 2.36-2.46 (m, 1H), 2.08-2.21 (m, 1H); MS(ESI) 413[M-H], 415[M+H]. Analytical HPLC; Capcell Pak C18, 30% acetonitrile: 70% 0.1% aqueous TFA.51 trans: 49 cis. FTIR (ATR) 1650, 1720 cm−1. Anal. (C20H18N2O4S2) calc. C, 57.95; H, 4.38; N, 6.76. obs. C, 57.59; H, 4.34; N, 6.56.

Provenance & Evidence