Chlorotrimethylsilane → Deoxycytidine

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

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.

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