The reaction of 2,6-dichloro-9-(2',3',5'-tri-O-acetyl-beta-D-ribofuranosyl)-9H-purine (I) with O-methylhydroxylamine in hot dioxane gives 2',3',5'-tri-O-acetyl-2-chloro-N-methoxy-adenosine (II), which is then treated with sodium methoxide in methanol.

The cyclization of ribofuranoside (I) with trimethylsilyl acetylene (II) by means of NBS in DMF gives the trimethylsilylisoxazole (III), which is desilylated with NaOH in methanol yielding the isoxazole (IV). Elimination of the isopropylidene protecting group of (IV) by passing through a Dowex 50 H+ column affords the dihydroxy compound (V), which is benzoylated with benzoyl chloridde and DMAP in pyridine giving the dibenzoyl derivative (VI). The condensation of (VI) with 2,6-dichloro-9H-purine (VII) in refluxing hexamethyldisilazane (HMDA) provides the purine derivative (VIII), which is treated with 0-methylhydroxylamine and triethylamine in refluxing dioxane yielding the adenosine derivative (IX). Finally, this compound is debenzoylated with ammonia in methanol.

Reaction of dichloropurine (I) with O-methylhydroxylamine hydrochloride and N-ethyldiisopropylamine in dioxan at 50 C yielded the N-methoxy derivative (II). Subsequent treatment with a catalytic amount of NaOMe in methanol at room temperature provided a mixture of 2-chloro-N-methoxyadenosine (III) and monoacetate (IV), which were separated by flash chromatography. Treatment of monoacetate (IV) with alpha-acetoxyisobutyryl bromide (V) in acetonitrile at low temperature yielded bromide (VI), which on further treatment with 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) gave the didehydrocompound (VII). Finally, reaction with NaOMe in methanol at 50 C provided the title compound.