Disclosed are methods for preparing 2-alkynyladenosine derivatives of formula A: or a stereoisomer, pharmaceutically acceptable salt, hydrate, solvate, acid salt hydrate or isomorphic crystalline form thereof, the method comprising the step of: contacting 2-iodoadenosine-5'-N-ethyluronamide with a compound of formula B: wherein Z is --C(.dbd.O)OR or --CH.sub.2C(.dbd.O)R, where R is a C.sub.1 to C.sub.5 alkyl, preferably The methods are useful for preparing 2-alkynyladenosine derivatives that are, in certain embodiments, adenosine receptor agonists.