Chloroacetyl isocyanate → 1H-Imidazole-2-methanol, 5-((3,5-dichlorophenyl)thio)-4-(1-methylethyl)-1-(3-quinolinylmethyl)-, carbamate (ester)

Participants

Reaction Conditions

Reaction Steps

In 5 ml of tetrahydrofuran was dissolved 223 mg (0.50 mmol)of 2-hydroxymethyl-5-(3,5-dichlorophenylthio)-4-isopropyl-1-(quinolin-3-ylmethyl)-1H-imidazole (109), followed by dropwise addition of 72 mg (0.60 mmol)of chloroacetylisocyanate with stirring at 0° C., and the mixture was stirred at room temperature for 30 minutes. After the reaction completion, the mixture was worked up. To the reaction mixture was added a saturated aqueous sodium bicarbonate solution, extracted with methylene chloride, the extract was washed with water and dried. The-solvent was distilled off under reduced pressure, and 2-chloroacetyl-carbamoyloxymethyl-5-(3,5-dichlorophenylthio)-4-isopropyl-1-(quinolin-3-ylmethyl)-1H-imidazole (110)suited to the next step of the reaction was obtained. mp 167-170° C. The crystals were dissolved in 20 ml of aqueous methanol, 40 mg of Zn powder was added, and the mixture was stirred at room temperature for 5 hours. After the reaction completion, the mixture was worked up. To the reaction mixture was added a saturated aqueous sodium hydrogen carbonate solution, and the insoluble material was removed by filtration under reduced pressure through Celite. The filtrate was concentrated, extracted with methylene chloride, the extract was washed with water and dried, and the solvent was distilled off. The residual crystals were washed with ethyl acetate and ether to give 195 mg of Compound I-128 (yield 78%). mp 214-216° C.

Provenance & Evidence