反应详情

温度

0 °C

2′-deoxycytidine monohydrochloride (3.955 g, 15 mmol) that had been subjected to azeotropic dehydration with pyridine (2×20 ml) was suspended in anhydrous pyridine (40 ml) and cooled to 0° C. under an argon gas stream. Chlorotrimethylsilane (9.5 ml, 75 mmol) was added and the mixture was stirred for 20 minutes. Benzoyl chloride-monomethoxypolyethylene glycol CH3O(CH2CH2O)kC6H4COCl (11.8 mmol, mPEG portion Mn=2000) prepared according to the method shown in Example 3′-1 was dissolved in anhydrous pyridine (50 ml) under an argon gas stream, and was added to the previously prepared reaction solution and stirred at room temperature for 2.5 hours. After cooling to 0° C., distilled water (10 ml) was added to the reaction mixture, and after removing the solvent under reduced pressure for concentration to approximately 1/2, it was recooled to 0° C., concentrated ammonium hydroxide (10 ml) was added and the mixture was stirred for 15 minutes. The solvent was removed under reduced pressure, a saturated sodium bicarbonate aqueous solution (100 ml) was added, and extraction was performed with chloroform (3×100 ml). The organic layer was washed. with water (2×100 ml) and dried over anhydrous sodium sulfate. After filtration, the filtrate was condensed under reduced pressure and the residue was purified by silica gel column chromatography (chloroform/methanol=100/2→100/5) to obtain the PEG-modified 2′-deoxycytidine (5.470 g, 20% yield). The 1H-NMR of the obtained compound (400 MHz, CDCl3, TMS) was δ=9.00 (brs,1H,NH), 8.46 (d, J=8.0 Hz,1H,H6), 7.87 (d, J=8.8 Hz,2H,ArH), 7.52 (br,1H,H5), 6.98 (d, J=8.8 Hz,2H,ArH), 6.22 (t, J=5.6 Hz,1H,H1′), 4.58-4.50 (br,2H), 4.36-4.15 (m,3H), 4.10-3.41 (m), 3.38 (s,3H,OCH3), 2.62-2.52 (m,1H,H2″), 2.37-2.23 (m,1H,H2′) ppm.

1. additionwas added to the previously prepared reaction solution
2. stirringstirred at room temperature for 2.5 hours
3. temperatureAfter cooling to 0° C.
4. distillationdistilled water (10 ml)
5. additionwas added to the reaction mixture
6. customafter removing the solvent under reduced pressure
7. concentrationfor concentration to approximately 1/2, it
8. customwas recooled to 0° C.
9. additionconcentrated ammonium hydroxide (10 ml) was added
10. stirringthe mixture was stirred for 15 minutes
11. customThe solvent was removed under reduced pressure
12. additiona saturated sodium bicarbonate aqueous solution (100 ml) was added
13. extractionextraction
14. washThe organic layer was washed
15. dry with materialwith water (2×100 ml) and dried over anhydrous sodium sulfate
16. filtrationAfter filtration
17. customcondensed under reduced pressure
18. customthe residue was purified by silica gel column chromatography (chloroform/methanol=100/2→100/5)