Uracil → HCID 69094268, compound

Bis(trimethylsilyl)acetamide (BSA; 29.2 mL, 118 mmol) was added to a mixture of 6 (14.0 g, 23.1 mmol) and uracil (5.99 g, 53.4 mmol) in anhydrous acetonitrile (300 mL). The reaction mixture was refluxed for 1 hour and the clear solution was allowed to cool down to room temperature. Tinchloride (11.55 mL, 99 mmol) was added dropwise at room temperature and the mixture was further stirred for 1 hour. The mixture was then stirred at reflux for 1.5 hour and again cooled to room temperature. Ethyl acetate (250 mL) was added, followed by saturated aqueous NaHCO3 (250 mL) and the mixture was stirred for 15 minutes. After filtration through Celite, the organic layer was separated and washed with saturated aqueous NaHCO3 (250 mL). The combined aqueous layer was extracted with ethyl acetate (250 mL) and the combined organic layer was dried (MgSO4), filtered and evaporated to dryness under reduced pressure. The resulting yellow oil was dissolved in methanol and 25% sodium methanolate (25 mL) was added. Stirring continued overnight. More 25% sodium methanolate (15 mL) was added and stirring was continued overnight. Acetic acid (30 mL) was added and the solvent was removed. The residue was purified by column chromategraphy with heptane/ethyl acetate 50:50 to 100% ethyl acetate. Intermediate 7 (9.38 g, 76%) was obtained as a colorless oil. HPLC Condition A, Rt: 2.49 min, m/z=465 (M+H)+. 1H NMR (400 MHz, CDCl3) δ ppm 8.39 (1H, NH), 7.75 (d, 1H, J=8.0 Hz), 7.22-7.43 (m, 10H), 6.05 (s, 1H), 5.71-5.84 (m, 1H), 5.35 (d, 1H, J=8.0 Hz), 5.00-5.11 (m, 2H), 4.70 (d, 1H, J=11.5 Hz), 4.53 (d, 1H, J=11.5 Hz), 4.47 (d, 1H, J=11.1 Hz), 4.47 (d, 1H, J=11.1 Hz), 4.11-4.16 (m, 1H), 4.04 (d, 1H, J=8.0 Hz), 3.81-3.87 (m, 1H), 3.45-3.52 (m, 1H), 3.17 (bs, OH), 2.15-2.33 (m, 2H).

1. temperatureThe reaction mixture was refluxed for 1 hour
2. stirringThe mixture was then stirred
3. temperatureat reflux for 1.5 hour
4. temperatureagain cooled to room temperature
5. stirringthe mixture was stirred for 15 minutes
6. filtrationAfter filtration through Celite
7. customthe organic layer was separated
8. washwashed with saturated aqueous NaHCO3 (250 mL)
9. extractionThe combined aqueous layer was extracted with ethyl acetate (250 mL)
10. dry with materialthe combined organic layer was dried (MgSO4)
11. filtrationfiltered
12. customevaporated to dryness under reduced pressure
13. dissolutionThe resulting yellow oil was dissolved in methanol
14. addition25% sodium methanolate (25 mL) was added
15. stirringStirring
16. waitcontinued overnight
17. additionMore 25% sodium methanolate (15 mL) was added
18. stirringstirring
19. waitwas continued overnight
20. additionAcetic acid (30 mL) was added
21. customthe solvent was removed
22. customThe residue was purified by column chromategraphy with heptane/ethyl acetate 50

ORD record

ord-54b6b71b8c7048558e1de994054f94fd

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09012428B2