Hydrochloric Acid → 9H-Purin-6-amine, 9-(3-deoxy-beta-D-threo-pentofuranosyl)-

Temperature

-15 °C

Adenosine (5.0 g, 18.7 mmol) was suspended in dry pyridine (50 ml) and colled to -15° C. To the suspension was added pivaloyl chloride (7.0 ml, 56.8 mmol), and the mixture was first stirred at -15° C. for 1.5 hour, and then at 0° C. for 2 hours. Methanesulfonyl chloride (4.3 ml, 55.6 mmol) was added dropwise to the reaction mixture under ice cooling. The mixture was stirred at room temperature for 3 hours, then cooled with ice again. A small amount of water was added and stirred for 30 minutes. The reaction mixture was extracted with chloroform-ether. The organic layer was washed with saturated aqueous sodium bicarbonate solution and then with water, and dried over magnesium sulfate. The drying agent was removed by filtration and the filtrate was concentrated in vacuo to dryness to give amorphous substances. The remaining pyridine was removed by repeated co-evaporation with toluene. The residue was dissolved in methanol (150 ml), cooled to -15° C., after which sodium methoxide (8.1 g, 150 mmol) and sodium borohydride (2.5 g, 66.1 mmol) were added. The mixture was first stirred at room temperature for 14 hours and then at 50° C. for 3 hours. After ice cooling, a small amount of acetone was added to the reaction mixture to decompose an excess of NaBH4. Concentrated hydrochloric acid was gradually added to neutralize the solution. Ethanol was added to the mixture, which was then concentrated under reduced pressure to remove water completely. The residue was suspended in chloroform-methanol and applied to a silica gel column (250 g). Elution with chloroform-methanol (8:1→5:1) gave compound A'3 as oils, which were then crystallized from ethanol-ether. Yield: 2.7 g (57%).

1. customcolled to -15° C
2. waitat 0° C. for 2 hours
3. stirringThe mixture was stirred at room temperature for 3 hours
4. temperaturecooled with ice again
5. stirringstirred for 30 minutes
6. extractionThe reaction mixture was extracted with chloroform-ether
7. washThe organic layer was washed with saturated aqueous sodium bicarbonate solution
8. dry with materialwith water, and dried over magnesium sulfate
9. customThe drying agent was removed by filtration
10. concentrationthe filtrate was concentrated in vacuo to dryness
11. customto give amorphous substances
12. customThe remaining pyridine was removed
13. dissolutionThe residue was dissolved in methanol (150 ml)
14. temperaturecooled to -15° C.
15. stirringThe mixture was first stirred at room temperature for 14 hours
16. waitat 50° C. for 3 hours
17. concentrationwas then concentrated under reduced pressure
18. customto remove water completely
19. washElution with chloroform-methanol (8:1→5:1)
20. customgave compound A'3 as oils, which
21. customwere then crystallized from ethanol-ether

ORD record

ord-167ae1d98431483aaf54628cd56c2f8a

Source dataset

uspto-grants-1995_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05476931