The acetylation of uridine (I) with acetic anhydride gives the 2',3',5'-triacetyl derivative (II), which is treated with SOCl2 and sodium ethoxide yielding the 4-ethoxypyrimidinone (III). The partial protection of (III) with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane (IV) yields the silylated compound (V), which is oxidized with oxalyl chloride to the silylated furanone (VI). The reaction of (VI) with fluoromethyl phenyl sulfone (A) by means of diethyl chlorophosphate (B) and lithium hexamethyldisylazide in THF affords the fluorovinyl sulfone (VII) as a mixture of (E) and (Z) isomers that is separated by flash chromatography. The (Z)-isomer (VII) is treated with tributyl tin hydride and AIBN in refluxing benzene to give the fluorovinyl stannane (VIII), which is finally treated with CsF and NH3 in refluxing methanol to afford the target compound.

The protection of cytidine (I) with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane (II) and dimethylformamide dimethylacetal (A) in pyridine gives the fully protected cytidine (III), which is oxidized with oxalyl chloride in DMSO/dichloromethane yielding the 2'-deoxy-2'-oxo derivative (IV). The reaction of (IV) with fluoromethyl phenyl sulfone (B) by means of diethyl chlorophosphate and lithium hexamethyldisylazide in THF affords the fluorovinyl sulfone (V) as a mixture of (E) and (Z) isomers that is separated by flash chromatography. The (Z)-isomer (V) is treated with tributyl tin hydride and AIBN in refluxing benzene to give the fluorovinyl stannane (VI), which is finally treated with KF in refluxing methanol to afford the target compound.

The protection of cytidine (I) with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane (II) and dimethylformamide dimethylacetal (A) in pyridine gives the fully protected cytidine (III), which is oxidized with oxalyl chloride in DMSO/dichloromethane yielding the 2'-deoxy-2'-oxo derivative (IV). The reaction of (IV) with fluoromethyl phenyl sulfone (B) by means of diethyl chlorophosphate and lithium hexamethyldisylazide in THF affords the fluorovinyl sulfone (V) as a mixture of (E) and (Z) isomers that is separated by flash chromatography. The (Z)-isomer (V) is treated with tributyl tin hydride and AIBN in refluxing benzene to give the fluorovinyl stannane (VI), which is finally treated with KF in refluxing methanol to afford the target compound.

The protection of cytidine (I) with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane (II) and dimethylformamide dimethylacetal (A) in pyridine gives the fully protected cytidine (III), which is oxidized with oxalyl chloride in DMSO/dichloromethane yielding the 2'-deoxy-2'-oxo derivative (IV). The reaction of (IV) with fluoromethyl phenyl sulfone (B) by means of diethyl chlorophosphate and lithium hexamethyldisylazide in THF affords the fluorovinyl sulfone (V) as a mixture of (E) and (Z) isomers that is separated by flash chromatography. The (Z)-isomer (V) is treated with tributyl tin hydride and AIBN in refluxing benzene to give the fluorovinyl stannane (VI), which is finally treated with KF in refluxing methanol to afford the target compound.

The acetylation of uridine (I) with acetic anhydride gives the 2',3',5'-triacetyl derivative (II), which is treated with SOCl2 and sodium ethoxide yielding the 4-ethoxypyrimidinone (III). The partial protection of (III) with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane (IV) yields the silylated compound (V), which is oxidized with oxalyl chloride to the silylated furanone (VI). The reaction of (VI) with fluoromethyl phenyl sulfone (A) by means of diethyl chlorophosphate (B) and lithium hexamethyldisylazide in THF affords the fluorovinyl sulfone (VII) as a mixture of (E) and (Z) isomers that is separated by flash chromatography. The (Z)-isomer (VII) is treated with tributyl tin hydride and AIBN in refluxing benzene to give the fluorovinyl stannane (VIII), which is finally treated with CsF and NH3 in refluxing methanol to afford the target compound.

The acetylation of uridine (I) with acetic anhydride gives the 2',3',5'-triacetyl derivative (II), which is treated with SOCl2 and sodium ethoxide yielding the 4-ethoxypyrimidinone (III). The partial protection of (III) with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane (IV) yields the silylated compound (V), which is oxidized with oxalyl chloride to the silylated furanone (VI). The reaction of (VI) with fluoromethyl phenyl sulfone (A) by means of diethyl chlorophosphate (B) and lithium hexamethyldisylazide in THF affords the fluorovinyl sulfone (VII) as a mixture of (E) and (Z) isomers that is separated by flash chromatography. The (Z)-isomer (VII) is treated with tributyl tin hydride and AIBN in refluxing benzene to give the fluorovinyl stannane (VIII), which is finally treated with CsF and NH3 in refluxing methanol to afford the target compound.

The acetylation of uridine (I) with acetic anhydride gives the 2',3',5'-triacetyl derivative (II), which is treated with SOCl2 and sodium ethoxide yielding the 4-ethoxypyrimidinone (III). The partial protection of (III) with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane (IV) yields the silylated compound (V), which is oxidized with oxalyl chloride to the silylated furanone (VI). The reaction of (VI) with fluoromethyl phenyl sulfone (A) by means of diethyl chlorophosphate (B) and lithium hexamethyldisylazide in THF affords the fluorovinyl sulfone (VII) as a mixture of (E) and (Z) isomers that is separated by flash chromatography. The (Z)-isomer (VII) is treated with tributyl tin hydride and AIBN in refluxing benzene to give the fluorovinyl stannane (VIII), which is finally treated with CsF and NH3 in refluxing methanol to afford the target compound.

The acetylation of uridine (I) with acetic anhydride gives the 2',3',5'-triacetyl derivative (II), which is treated with SOCl2 and sodium ethoxide yielding the 4-ethoxypyrimidinone (III). The partial protection of (III) with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane (IV) yields the silylated compound (V), which is oxidized with oxalyl chloride to the silylated furanone (VI). The reaction of (VI) with fluoromethyl phenyl sulfone (A) by means of diethyl chlorophosphate (B) and lithium hexamethyldisylazide in THF affords the fluorovinyl sulfone (VII) as a mixture of (E) and (Z) isomers that is separated by flash chromatography. The (Z)-isomer (VII) is treated with tributyl tin hydride and AIBN in refluxing benzene to give the fluorovinyl stannane (VIII), which is finally treated with CsF and NH3 in refluxing methanol to afford the target compound.

The acetylation of uridine (I) with acetic anhydride gives the 2',3',5'-triacetyl derivative (II), which is treated with SOCl2 and sodium ethoxide yielding the 4-ethoxypyrimidinone (III). The partial protection of (III) with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane (IV) yields the silylated compound (V), which is oxidized with oxalyl chloride to the silylated furanone (VI). The reaction of (VI) with fluoromethyl phenyl sulfone (A) by means of diethyl chlorophosphate (B) and lithium hexamethyldisylazide in THF affords the fluorovinyl sulfone (VII) as a mixture of (E) and (Z) isomers that is separated by flash chromatography. The (Z)-isomer (VII) is treated with tributyl tin hydride and AIBN in refluxing benzene to give the fluorovinyl stannane (VIII), which is finally treated with CsF and NH3 in refluxing methanol to afford the target compound.

The acetylation of uridine (I) with acetic anhydride gives the 2',3',5'-triacetyl derivative (II), which is treated with SOCl2 and sodium ethoxide yielding the 4-ethoxypyrimidinone (III). The partial protection of (III) with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane (IV) yields the silylated compound (V), which is oxidized with oxalyl chloride to the silylated furanone (VI). The reaction of (VI) with fluoromethyl phenyl sulfone (A) by means of diethyl chlorophosphate (B) and lithium hexamethyldisylazide in THF affords the fluorovinyl sulfone (VII) as a mixture of (E) and (Z) isomers that is separated by flash chromatography. The (Z)-isomer (VII) is treated with tributyl tin hydride and AIBN in refluxing benzene to give the fluorovinyl stannane (VIII), which is finally treated with CsF and NH3 in refluxing methanol to afford the target compound.

The protection of labeled cytidine (I) with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane (II) and dimethylformamide dimethylacetal (A) in pyridine gives the fully protected cytidine (III), which is oxidized with oxalyl chloride in DMSO/dichloromethane yielding the 2'-deoxy-2'-oxo derivative (IV). The reaction of (IV) with fluoromethyl phenyl sulfone (B) by means of diethyl chlorophosphate and lithium hexamethyldisylazide in THF affords the fluorovinyl sulfone (V) as a mixture of (E) and (Z) isomers that is separated by flash chromatography. The (Z)-isomer (V) is treated with tributyl tin hydride and AIBN in refluxing benzene to give the fluorovinyl stannane (VI), which is finally treated with KF in refluxing methanol to afford the labeled target compound.

The protection of cytidine (I) with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane (II) and dimethylformamide dimethylacetal (A) in pyridine gives the fully protected cytidine (III), which is oxidized with oxalyl chloride in DMSO/dichloromethane yielding the 2'-deoxy-2'-oxo derivative (IV). The reaction of (IV) with labeled fluoromethyl phenyl sulfone (V) by means of diethyl chlorophosphate (B) and lithium hexamethyldisylazide in THF affords the fluorovinyl sulfone (VI) as a mixture of (E) and (Z) isomers that is separated by flash chromatography. The (Z)-isomer (VI) is treated with tributyl tin hydride and AIBN in refluxing benzene to give the fluorovinyl stannane (VII), which is finally treated with KF in refluxing methanol to afford the labeled target compound.

The acetylation of (E)-2'-deoxy-2'-(fluoromethylene)cytidine (I) with acetyl chloride gives the diacetate (II), which is iodinated with iodine and silver trifluoroacetate in dioxane yielding the 5-iodo derivative (III). The hydrogenation of (III) with tritium over Rh/Al2O3 affords the tritiated diacetyl target compound (IV), which is finally hydrolyzed with K2CO3 in methanol.

A new synthesis of tezacitabine has been described: Protection of cytidine (I) with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane (II) in pyridine gives the protected cytidine (III), which is oxidized with trifluoroacetic anhydride (TFAA)/DMSO in THF and treated with TEA to yield the 2'-deoxy-2'-oxocytidine derivative (IV). Condensation of (IV) with fluoromethyl phenyl sulfone (V) by means of diethyl chlorophosphate and lithium hexamethyldisilazide in THF affords the fluorovinyl sulfone (VI) as a mixture of (E)- and (Z)-isomers that is separated by flash chromatography. The desired (Z)-isomer (VI) is treated with tributyl tin hydride and AIBN in refluxing benzene to give the fluorovinyl stannane (VII), which is finally treated with KF in refluxing methanol.