Hydrochloric Acid → HCID 136025160, compound

Guanosine (5.0 g, 17.7 mmol) was suspended in dry pyridine (50 ml). To the suspension was added pivaloyl chloride (9.8 ml) 79.6 mmol) under ice cooling, and the mixture was then stirred at room temperature for 45 minutes. After ice cooling, methanesulfonyl chloride (4.1 ml, 53.0 mmol) was added dropwise to the reaction mixture, after which it was first stirred at 0° C. for 1 hour and then at room temperature for 3 hours. The reaction mixture was cooled with iced water and a small amount of water was added thereto and the mixture was stirred for 30 minutes. The reaction mixture was extracted with chloroform-ether and the organic layer was washed with saturated aqueous sodium bicarbonate and then with water, and dried over magnesium sulfate. The drying agent was removed by filtration and the filtrate was evaporated. The residue was dissolved in toluene and the solvent was evaporated under reduced pressure. This procedure was repeated several times to completely remove the remaining pyridine.. The residue was dissolved in methanol (120 ml). Sodium methoxide (7.6 g, 140.7 mmol) and sodium borohydride (2.7 g, 71.4 mmol) were added to the solution, after which it was first stirred at room temperature for 1 hour and then at 50° C. for 5 hours. After ice cooling, a small amount of acetone was added to decompose an excess of NaBH4. Methanol (100 ml) was added to the mixture, after which it was concentrated to 1/2 volume. This procedure was repeated to remove methyl borate thus produced as a by-product. The reaction mixture was again cooled with ice, and concentrated hydrochloric acid was gradually added to neutralize. Then, water was added and the mixture was concentrated under reduced pressure. The residue from which alcohol had been removed completely was suspended in water (about 150 ml), and applied to HP-20 (DIAION: 600 ml made up with water, Mitsubishi Chemical Industries Ltd.) column. Water (about 1.5 l) was passed through the column to elute inorganic salts, and the product was then eluted with 5% methanol-water followed with 5% methanol--0.1M ammonia water. Fractions containing compound G3 were concentrated to dryness under reduced pressure and the-residue was recrystallized from methanol to give colorless crystals (1.31 g, 27.8%). The mother liquor was dried up under reduced pressure, again subjected to HP-20 column chromatography (300 ml) and followed by the same procedures mentioned above to give compound G3 (0.55 g, 11.6%).

1. stirringafter which it was first stirred at 0° C. for 1 hour
2. waitat room temperature for 3 hours
3. stirringthe mixture was stirred for 30 minutes
4. extractionThe reaction mixture was extracted with chloroform-ether
5. washthe organic layer was washed with saturated aqueous sodium bicarbonate
6. dry with materialwith water, and dried over magnesium sulfate
7. customThe drying agent was removed by filtration
8. customthe filtrate was evaporated
9. dissolutionThe residue was dissolved in toluene
10. customthe solvent was evaporated under reduced pressure
11. customto completely remove the remaining pyridine
12. dissolutionThe residue was dissolved in methanol (120 ml)
13. stirringafter which it was first stirred at room temperature for 1 hour
14. waitat 50° C. for 5 hours
15. concentrationafter which it was concentrated to 1/2 volume
16. customto remove methyl borate
17. customthus produced as a by-product
18. additionwas gradually added
19. concentrationthe mixture was concentrated under reduced pressure
20. customThe residue from which alcohol had been removed completely
21. washto elute inorganic salts
22. washthe product was then eluted with 5% methanol-water
23. additionFractions containing compound G3
24. concentrationwere concentrated to dryness under reduced pressure and the-residue
25. customwas recrystallized from methanol

ORD record

ord-71df0cea554b4ae89c9a90d01f1750a0

Source dataset

uspto-grants-1995_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05476931