Dichloromethane → 7-Amino-1-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-1,3-aza-phospholo[4,5-d]pyrimidine

A mixture of 7-amino-1H-1,3-azaphospholo[4,5-d]pyrimidine (compound 10, 0.3 g, 1.97 mmol) in 1,1,1,3,3,3-hexamethyldisilazane (HMDS, 5 mL), pyridine (5 mL) and ammonium sulfate (50 mg) was heated under reflux for 18 h. The reaction mixture was allowed to cool to room temperature and the excess of HMDS and pyridine were evaporated in vacuo. The silyl derivative of compound 10 was dried under high vacuum for 3 h. The dried material was dissolved in 1,2-dichloroethane (30 mL) to which 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose (1.28 g, 2.4 mmol) was added. The mixture was cooled in an ice bath. A solution of SnCl4 in dichloromethane (1 M, 2.8 mL, 2.8 mmol) was added keeping the flask under an argon atmosphere. After stirring the mixture in the ice bath for 4 h, the ice bath was removed and the reaction was continued at ambient temperature for 18 h. Methanol (10 mL) was added and after 10 min it was diluted with dichloromethane (100 mLL). The organic layer was washed with saturated sodium hydrogen carbonate solution (50 mL) and the resultant emulsion was filtered through a Celite pad. Organic layer was separated and the aqueous layer was extracted with dichloromethane (2×50 mL). The combined organic layer was dried (Na2SO4) and evaporated. The solid thus obtained was crystallized from a mixture of ethyl acetate and methanol to give 0.65 g (56%) of the title compound, mp 248-250° C. (dec). 1H nmr (DMSO-d6): δ 4.85(m,2 t C5H2), 4.96 (m, 1 H, C4'H), 6.01 (m, 1 H, C3'H), 6.19 (m, 1 H, C2'H), 6.51 (d, 1 H, C1'H), 7.44-8.05 (m, 15 H, 3Bz), 8.44 and 8.47 (2s, 2 H, NH2), 8.75 (d, 1 H, C5H), and 8.95 (d, 1 H, J =57 Hz, C2H). Anal. Calcd. for C31H25N4O7P.0.5 H2O: C, 61.49; H, 4.33; N, 9.25. Found: C, 61.61; H, 3.88; N, 9.21.

1. temperaturewas heated
2. temperatureunder reflux for 18 h
3. customthe excess of HMDS and pyridine were evaporated in vacuo
4. dry with materialThe silyl derivative of compound 10 was dried under high vacuum for 3 h
5. additionwas added
6. temperatureThe mixture was cooled in an ice bath
7. customthe ice bath was removed
8. additionMethanol (10 mL) was added and after 10 min it
9. additionwas diluted with dichloromethane (100 mLL)
10. washThe organic layer was washed with saturated sodium hydrogen carbonate solution (50 mL)
11. filtrationthe resultant emulsion was filtered through a Celite pad
12. customOrganic layer was separated
13. extractionthe aqueous layer was extracted with dichloromethane (2×50 mL)
14. dry with materialThe combined organic layer was dried (Na2SO4)
15. customevaporated
16. customThe solid thus obtained
17. customwas crystallized from a mixture of ethyl acetate and methanol

ORD record

ord-f8f0f24ba36c48299ede36032093ac7e

Source dataset

uspto-grants-2000_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06069132