HCID 135855931, compound → HCID 136401244, compound

Participants

Reaction Conditions

Reaction Steps

A 3 liter, four-necked round-bottomed flask equipped with an air driven stirrer, a thermostat-controlled heating mantle, a reflux condenser vented through a bleach trap and a fine fritted gas inlet tube was charged with 42.7 g (0.127 mole) of (1'S, 3'S, 4'S)-2-amino-1,9-dihydro-9-[3,4-dihydroxy-3-(hydroxymethyl)-1-cyclopentanyl]-6H-purin-6-one dimethylaminal of Formula (Ip) and 1.14 L of deionized water. The slurry was heated with stirring to 65° C. to form a homogeneous solution, then hydrogen sulfide gas was gently bubbled into the solution for 2 hours to precipitate osmium containing impurities. The gas inlet tube was removed, the condenser was connected to a nitrogen atmosphere and the reaction mixture was stirred at 65° C. After 22 hours, 600 ml of absolute ethanol was added to the warm reaction mixture and the solution was hot-filtered through a 2 inch pad (100 g) of diatomaceous earth in a hot, steam-jacketed filter funnel. The pad was washed with 500 mL of 1:1 ethanol-water. The combined filtrates were cooled to 25° C., then to 0° C. over 1.5 hr to induce crystallization. The crystals were collected by vacuum filtration. The filtrate volume was reduced in vacuo to 150 ml and a second crop of crystals was collected by vacuum filtration. The damp 47.0 g of first and second crops were combined with 1.95 L of 60:40 methanol-deionized water in a 3 L four-necked round-bottomed flask equipped with an air-driven stirrer, a reflux condenser vented to a bleach bath, a thermometer, and a fine fritted gas inlet tube. The solution was heated to 60° C. and hydrogen sulfide was gently bubbled into the stirred solution for 30 seconds. The solution was stirred for 30 minutes at 60° C., then hot filtered through a 2 inch pad (100 g) of diatomaceous earth in a hot, steam-jacketed filter funnel. The pad was washed with 250 ml of 1:1 ethanol:deionized water. The filtrate volume was reduced in vacuo to 550 ml, then cooled to 0° C. to induce crystallization. The crystals were collected by vacuum filtration. The crystals were washed with 250 ml of absolute ethanol, then 350 ml of 9:1 acetonitrile-ethanol to assist in drying. The crystals were transferred to 500 ml round-bottomed flask and dried in vacuo (0.5 mm, 25° C., 5 hours) to provide 32.2 g of (1'S, 3'S, 4'S)-2-amino-1,9-dihydro-9-[3,4-dihydroxy-3-(hydroxymethyl)-1-cyclopentanyl]-6H-purin-6-one hydrate in 90% yield. NMR (200 MHz, 6 d-DMSO) δ10.6 (s, 1H), 7.8 (s, 1H), 6.4 (s, 2H), 4.9 (m, 1H), 4.8 (m, 2H), 4.3 (s, 1H), 4.2 (t, J=6 Hz, 1H), 3.4 (m, 2H) and 2.1 ppm (m, 4H).

Provenance & Evidence