Efficient formation of 4,6-disubstituted pyrrolo[2,3-d]pyrimidines: a novel route to TWS119, a glycogen synthase kinase-3β inhibitor

A concise synthesis of 4,6-disubstituted pyrrolo[2,3-d]pyrimidines is described. The key step involves the formation of an ether or thioether linkage along with concurrent ring closure in one-pot to yield the desired product in only two steps from a common intermediate. The reaction is chemoselective to incorporate phenol, thiophenol, and thiol. This method enabled efficient production of TWS119, a glycogen synthase kinase-3β inhibitor.