Carbon Dioxide → HCID 69662067, compound

Participants

Reaction Steps

Compound 35a (3.95 g, 9.90 mmol) obtained in Example 35 was dissolved in tetrahydrofuran (100 mL), to the solution was added a 1.50 mol/L solution (9.9 mL) of lithium diisopropylamide (14.9 mmol, 1.5 equivalents) in cyclohexane at −78° C., and then the mixture was stirred for 1 hour. Into the reaction solution was poured carbon dioxide generated from dry ice and the mixture was stirred at room temperature for 1 hour. To the reaction solution was added 1 mol/L aqueous hydrochloric acid and the mixture was extracted with chloroform. The organic layer was washed with saturated aqueous sodium chloride and dried. The solvent was evaporated, and the residue was purified by silica gel column chromatography (chloroform:methanol=95:5 to 10:1). To the residue were added acetone and diethyl ether, and the deposited crystals were collected by filtration to obtain (R)-1,8-dibenzyl-2-carboxy-7,8-dihydro-4-(n-propyl)-1H-imidazo[2,1-i]purin-5(4H)-one (Compound 47a, 1.13 g, 26%). To Compound 47a (740 mg, 1.67 mmol) was added thionyl chloride (10.0 mL, 137 mmol, 82 equivalents) and the mixture was stirred at 60° C. for 2 hours. The reaction solution was concentrated under reduced pressure, and then to the reaction residue was added methanol (3 mL). The mixture was concentrated and the residue was directly purified by silica gel column chromatography (chloroform:methanol=95:5) to obtain the title compound (211 mg, 28%).

Provenance & Evidence