Benzoyl chloride → HCID 20610787, compound

Temperature

0 °C

To a solution of nucleoside 64 (232.7 mg, 0.66 mmol) in anhydrous acetonitrile (3 cm3) was added a solution of 1,2,4-triazole (420 mg, 6.1 mmol) and POCl3 (0.12 cm3, 1.3 mmol) in anhydrous acetonitrile (5 cm3). The reaction mixture was cooled to 0° C. and anhydrous triethylamine (0.83 cm3) was added, whereupon the mixture was kept for 90 min at room temperature. Triethylamine (0.54 cm3) and water (0.14 cm3) was added, and the reaction mixture was stirred for 10 min and evaporated under reduced pressure. The residue was dissolved in EtOAc and washed with a saturated aqueous solution of sodium hydrogencarbonate (2×9 cm3) and water (9 cm3). The aqueous phase was extracted with dichloromethane (3×20 cm3). The combined organic phase was evaporated under reduced pressure and the residue was redissolved in dioxane (4 cm3), whereupon 32% aqueous ammonia (0.7 cm3) was added. After stirring for 3 h, the reaction mixture was evaporated under reduced pressure and coevaporated with anhydrous pyridine. The residue was dissolved in anhydrous pyridine (3.6 cm3) and benzoyl chloride (0.42 cm3, 3.6 mmol) was added. After stirring for 2 h, the reaction was quenched with water (1 cm3) and the reaction mixture was evaporated under reduced pressure. The residue was then redissolved in EtOAc and washed with water (3×7 cm3). The organic phase was evaporated to dryness under reduced pressure, and the residue was dissolved in pyridine/methanol/water (13:6:1, v/v/v, 14 cm3) at 0° C., and a 2M solution of NaOH in pyridine/methanol/water (13:6:1, v/v/v, 7 cm3) was added. After stirring for 20 min, the reaction mixture was neutralised using a 2M solution of HCl in dioxane, and the reaction mixture was evaporated under reduced pressure. The residue was purified by silica column chromatography using dichloromethane/methanol (95:5, v/v) as eluent to give nucleoside 65 as a yellow foam (94.6 mg, 38%). δH (CD3OD) 8.21 (1H, br, s), 8.02 (1H, m), 7.84-7.9 (1H, m), 7.41-7.58 (4H, m), 5.61 (1H, s), 4.36 (1H, s), 4.10 (1H, s), 3.98 (1H, d, J 8.0), 3.94 (2H, s), 3.78 (1H, d, J 7.9), 2.11 (3H, d, J 1.0). δC (CD3OD, selected signals) 133.66, 132.90, 130.63, 129.50, 129.28, 128.65, 90.71, 88.86, 80.57, 72.47, 70.22, 57.53, 14.01. FAB-MS m/z 374 [M+H]+.

1. customevaporated under reduced pressure
2. dissolutionThe residue was dissolved in EtOAc
3. washwashed with a saturated aqueous solution of sodium hydrogencarbonate (2×9 cm3) and water (9 cm3)
4. extractionThe aqueous phase was extracted with dichloromethane (3×20 cm3)
5. customThe combined organic phase was evaporated under reduced pressure
6. dissolutionthe residue was redissolved in dioxane (4 cm3)
7. additionwhereupon 32% aqueous ammonia (0.7 cm3) was added
8. stirringAfter stirring for 3 h
9. customthe reaction mixture was evaporated under reduced pressure
10. dissolutionThe residue was dissolved in anhydrous pyridine (3.6 cm3)
11. stirringAfter stirring for 2 h
12. customthe reaction was quenched with water (1 cm3)
13. customthe reaction mixture was evaporated under reduced pressure
14. dissolutionThe residue was then redissolved in EtOAc
15. washwashed with water (3×7 cm3)
16. customThe organic phase was evaporated to dryness under reduced pressure
17. dissolutionthe residue was dissolved in pyridine/methanol/water (13:6:1, v/v/v, 14 cm3) at 0° C.
18. additiona 2M solution of NaOH in pyridine/methanol/water (13:6:1, v/v/v, 7 cm3) was added
19. stirringAfter stirring for 20 min
20. customthe reaction mixture was evaporated under reduced pressure
21. customThe residue was purified by silica column chromatography

ORD record

ord-fec2b57c8f23481184e9ccc946698485

Source dataset

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07572582B2