Water → N6-monomethoxytrityideoxyadenosine

Deoxyadenosine hydrate dA×H2O (50 g, 186 mmol.) was dried by coevaporation with pyridine and acetonitrile, and suspended in acetonitrile (200 ml). 1,1,1,3,3,3-hexamethyldisilazane (96 ml, 74.9 g, 465 mmol) was added and the resulting suspension was stirred over night at ambient temperature. The reaction mixture was concentrated to dryness by evaporation. The residue was dried by coevaporation with pyridine and dissolved in pyridine (260 ml). The solution was cooled on an ice bath and monomethoxytritylchloride (54.5 g, 177 mmol) was added. The reaction mixture was kept in a refrigerator at appr. 4° C. for 3 days. Additional portions of monomethoxytritylchloride (2 times 13.6 g, 45 mmol) were added successively in 24-hour time intervals while the reaction mixture was stirred at ambient temperature. The reaction mixture was treated with N-methylmorpholine (30 ml), stirred at ambient temperature for 30 minutes and evaporated to dryness. The residue was dissolved in ethylacetate (330 ml) and extracted with water (200 ml), 5% aqueous sodium hydrogencarbonate solution (2 times 200 ml) and brine (200 ml). The organic phase was concentrated to dryness by evaporation. The residue was dissolved in pyridine (100 ml) and water (20 ml), and stirred at 40° C. for 2 days. The solution was concentrated to a foam by evaporation. Purification by column chromatography on silica gel (acetone/dichloromethane, gradient elution) afforded the product in 99.9% purity by RP-HPLC (70 g, 67%). UV λmax 272 nm.

1. concentrationThe reaction mixture was concentrated to dryness by evaporation
2. dry with materialThe residue was dried by coevaporation with pyridine
3. dissolutiondissolved in pyridine (260 ml)
4. temperatureThe solution was cooled on an ice bath
5. stirringwas stirred at ambient temperature
6. stirringstirred at ambient temperature for 30 minutes
7. customevaporated to dryness
8. dissolutionThe residue was dissolved in ethylacetate (330 ml)
9. extractionextracted with water (200 ml), 5% aqueous sodium hydrogencarbonate solution (2 times 200 ml) and brine (200 ml)
10. concentrationThe organic phase was concentrated to dryness by evaporation
11. dissolutionThe residue was dissolved in pyridine (100 ml)
12. stirringwater (20 ml), and stirred at 40° C. for 2 days
13. concentrationThe solution was concentrated to a foam by evaporation
14. customPurification by column chromatography on silica gel (acetone/dichloromethane, gradient elution)
15. customafforded the product in 99.9% purity by RP-HPLC (70 g, 67%)

ORDレコード

ord-154ed53b8605499ca052b262443484f7

出典データセット

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08138330B2