Tonapofylline → 3-[4-(2,6-Dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]oct-1-yl]-propionic acid chloromethyl ester

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-[4-(2,6-Dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]oct-1-yl]-propionic acid (208 mg, 0.5 mmol), sodium bicarbonate (168 mg, 2 mmol), and tetra-n-butylammonium hydrogensulfate (17 mg, 0.05 mmol) in water (5 ml) and dichloromethane (5 ml) was stirred vigorously at 0° C. After 10 min, to the reaction mixture was added a solution of chloromethyl chlorosulfate in dichloromethane (1 ml) and allowed to ambient temperature and continued to stir vigorously. After a couple of hours, the organic layer was separated and washed with brine. The organic extracts were dried over sodium sulfate. After the solvent was removed in vacuo, the residue was purified by column chromatography on SiO2 using ethyl/hexane (1:5) as an eluent to give (200 mg, yield 86%) 3-[4-(2,6-Dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]oct-1-yl]-propionic acid chloromethyl ester. MS (M+1 465)

Provenance & Evidence