Water → 2-(1-{[6-Chloro-2-(methoxymethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-5-oxopyrrolidin-3-yl)ethyl 4-methylbenzenesulfonate

Participants

Reaction Conditions

Reaction Steps

4-[2-(benzyloxy)ethyl]-1-{[6-chloro-2-(methoxymethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}pyrrolidin-2-one a37 (300 mg, 0.69 mmol, 1 eq) is heated at 60° C. for 3 hours in trifluoroacetic acid (3 ml). The crude 1-{[6-chloro-2-(methoxymethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-(2-hydroxyethyl)pyrrolidin-2-one a38 is obtained after cooling and evaporation of the volatiles under reduced pressure. Dichloromethane (10 ml) is added to the residue, the mixture is cooled to 0° C., then tosyl chloride (158 mg, 0.828 mmol, 1.2 eq), triethyl amine (0.48 ml, 3.45 mmol, 5 eq) and 4-dimethylamino-pyridine (8 mg, 10 mol %,) are added at 0° C. The reaction is kept for 1 h at 0° C., then warmed up to room temperature and stirring is pursued for 2 days. After hydrolysis (H2O, 10 ml) and extraction with CH2Cl2 (4×10 ml), the cumulated organic layers are dried over MgSO4, filtered and evaporated under reduced pressure. The residue is purified by flash chromatography over silicagel (eluent: CH2Cl2/MeOH 97:3) to afford 308 mg of 2-(1-{[6-chloro-2-(methoxymethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-5-oxopyrrolidin-3-yl)ethyl 4-methylbenzenesulfonate a39.

Provenance & Evidence