Acetic Anhydride → HCID 86639019, compound

1-(2-Deoxy-β-D-ribofuranosyl)-4-[3-(6-trifluoroacetamidohexanamido)-1-propynyl]-2-nitropyrrole (394 mg, 803 μmol) was azeotroped three times with anhydrous pyridine in a 50 mL flask and dissolved in anhydrous pyridine (4 mL). To this solution, dimethoxytrityl chloride (286 mg, 844 μmol) was added and stirred at room temperature for 1.5 hours. The reaction mixture was added to ethyl acetate/water, and the aqueous layer was removed. The organic layer was washed with saturated aqueous sodium bicarbonate, dried over magnesium sulfate and then evaporated to remove the solvent. The resulting crude product was purified by silica gel column chromatography (0-0.5% CH3OH in CH2Cl2) to give a tritylated product as an amorphous substance (543 mg). 1-(2-Deoxy-5-O-dimethoxytrityl-β-D-ribofuranosyl)-4-[3-(6-trifluoroacetamidohexanamido)-1-propynyl]-2-nitropyrrole (542 mg, 684 μmol) was azeotroped three times with anhydrous pyridine in a 30 mL flask and dissolved in anhydrous pyridine (7 mL). To this solution, acetic anhydride (169 μL, 1.79 mmol) was added and stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride, dried over magnesium sulfate, and then evaporated to remove the solvent. The resulting crude product was dissolved in anhydrous dichloromethane (68 mL). To this solution, dichloroacetic acid (680 μL) was added while stirring at 0° C. and further stirred for 15 minutes. The reaction mixture was added to saturated aqueous sodium bicarbonate, and the aqueous layer was extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate and then evaporated to remove the solvent. The resulting oil was purified by silica gel column chromatography (2% CH3OH in CH2Cl2) to give the desired product as an amorphous substance (328 mg, 77%, yield for 2 steps).

1. customthe aqueous layer was removed
2. washThe organic layer was washed with saturated aqueous sodium bicarbonate
3. dry with materialdried over magnesium sulfate
4. customevaporated
5. customto remove the solvent
6. customThe resulting crude product was purified by silica gel column chromatography (0-0.5% CH3OH in CH2Cl2)
7. customto give a tritylated product as an amorphous substance (543 mg)
8. stirringstirred overnight at room temperature
9. washthe organic layer was washed with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride
10. dry with materialdried over magnesium sulfate
11. customevaporated
12. customto remove the solvent
13. dissolutionThe resulting crude product was dissolved in anhydrous dichloromethane (68 mL)
14. additionTo this solution, dichloroacetic acid (680 μL) was added
15. stirringwhile stirring at 0° C.
16. stirringfurther stirred for 15 minutes
17. additionThe reaction mixture was added to saturated aqueous sodium bicarbonate
18. extractionthe aqueous layer was extracted with dichloromethane
19. dry with materialThe combined organic layers were dried over magnesium sulfate
20. customevaporated
21. customto remove the solvent
22. customThe resulting oil was purified by silica gel column chromatography (2% CH3OH in CH2Cl2)

ORD record

ord-88d4c906d0e94bb7ad943e70dc73fc75

Source dataset

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08030478B2