Trimethylsilyl triflate → 5-Azacytidine

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Reaction Steps

34.7 mL of BSTFA are added to a suspension of 6.3 g of azacytosine in 126 mL of acetonitrile. The mixture is brought to 50° C. and it is stirred for 90 minutes. 11.35 mL of trimethylsilyltriflate and then a suspension of 29.0 g of 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose in 50 mL of acetonitrile are added to the limpid solution, in about ten minutes. Stirring is maintained for 75 minutes, it is cooled to ambient temperature and it is slowly poured onto a mixture constituted by 500 ml of dichloromethane and 330 ml of water into which 9.5 g of sodium bicarbonate had been previously dissolved. Stirring is carried out for 15 minutes and the pH is adjusted to pH=4.5 using acetic acid. The mixture is left to settle and phases are separated. The aqueous phase is washed twice using 125 ml of dichloromethane for each washing. The organic phases which are anhydrified by treating them with anhydrous calcium chloride are combined. Concentration is carried out at low pressure until a viscous residue is obtained. The residue is recovered with 250 mL of methanol, it is concentrated once again at low pressure until a viscous residue is obtained. 250 mL of methanol are added, it is heated to 50° C. and 15 mL of a 10% solution of sodium methylate in methanol are added. It is stirred for 1 hour, it is cooled to ambient temperature, it is stirred to complete precipitation and the solid is filtered by washing it on the filter with methanol. 5.4 g of azacitidine with HPLC purity (UV 254 nm) of 94.1% are obtained after drying at low pressure.

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