HCID 135855931, compound → HCID 136401244, compound

Temperature

65 °C

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).

1. customA 3 liter, four-necked round-bottomed flask equipped with an air
2. customa thermostat-controlled heating mantle, a reflux condenser vented through a bleach trap and a fine fritted gas inlet tube
3. temperatureThe slurry was heated
4. customto form a homogeneous solution
5. customhydrogen sulfide gas was gently bubbled into the solution for 2 hours
6. customto precipitate osmium containing impurities
7. customThe gas inlet tube was removed
8. stirringthe reaction mixture was stirred at 65° C
9. addition600 ml of absolute ethanol was added to the warm reaction mixture
10. filtrationthe solution was hot-filtered through a 2 inch pad (100 g) of diatomaceous earth in a hot, steam-jacketed filter funnel
11. washThe pad was washed with 500 mL of 1:1 ethanol-water
12. temperatureThe combined filtrates were cooled to 25° C.
13. waitto 0° C. over 1.5 hr to induce
14. customcrystallization
15. filtrationThe crystals were collected by vacuum filtration
16. filtrationa second crop of crystals was collected by vacuum filtration
17. customThe 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
18. customequipped with an air-driven stirrer, a reflux condenser
19. customvented to a bleach bath
20. temperatureThe solution was heated to 60° C.
21. customhydrogen sulfide was gently bubbled into the stirred solution for 30 seconds
22. stirringThe solution was stirred for 30 minutes at 60° C.
23. filtrationhot filtered through a 2 inch pad (100 g) of diatomaceous earth in a hot, steam-jacketed filter funnel
24. washThe pad was washed with 250 ml of 1:1 ethanol
25. temperaturecooled to 0° C.
26. customcrystallization
27. filtrationThe crystals were collected by vacuum filtration
28. washThe crystals were washed with 250 ml of absolute ethanol
29. customin drying
30. customThe crystals were transferred to 500 ml round-bottomed flask
31. customdried in vacuo (0.5 mm, 25° C., 5 hours)

ORD record

ord-5ae6bf3b22ad490db6e3dbd9d9cca03f

Source dataset

uspto-grants-1995_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05438132