2-(Chloromethyl)-4-isopropyl-6-methoxybenzo[D]isothiazol-3(2H)-one 1,1-dioxide → 2-[3-(4-morpholinylmethyl)-4-oxo-4-H-pyrido[1,2-a]pyrimidin-2yl]oxymethyl-4-isopropyl-6-methoxysaccharin

関与物質

反応手順

A mixture of 3-(4-morpholinylmethyl)pyrido[1,2-a]pyrimidine-2,4-dione hydrochloride (0.6 g) and potassium t-butoxide (0.49 g) in dimethylformamide (20 mL) was stirred at room temperature for five minutes. 2-Chloromethyl-4-isopropyl-6-methoxysaccharin (0.61 g) was added and stirring was continued at room temperature for one hour. The reaction mixture was diluted with water (50 mL) and extracted with dichloromethane (3×200 mL). The dichloromethane extract was dried over sodium sulfate and stripped of volatiles, finally under high vacuum. The crude product (780 mg) was combined with that (0.65 g) from another run at the same scale using sodium hydride (60% dispersion in mineral oil, 0.19 g) instead of potassium t-butoxide and purified by column chromatography on silica gel with dichloromethane-methanol (95:5) as eluant affording 2-[3-(4-morpholinylmethyl)-4-oxo-4-H-pyrido[1,2-a]pyrimidin-2yl]oxymethyl-4-isopropyl-6-methoxysaccharin (500 mg, 23% yield), part of which was recrystallized from ethanol (m.r. 177°-180° C.).

情報源と証拠