Process for the preparation of disubstituted acetylenes bearing heteroaromatic and heterobicyclic groups

摘要

A process for the preparation of a disubstituted acetylene bearing heteroaromatic and heterobicyclic groups of formula I is provided wherein X is S, O, or NR¹ wherein R¹ is hydrogen or a C₁-C₆ straight or branched alkyl group; R is hydrogen or a C₁-C₆ straight or branched alkyl group; A is a substituted or unsubstituted pyridinyl, thienyl, furyl, pyridazinyl, pyrimidinyl or pyrazinyl group; n is 0-4; and B is H, -COOH, -CH₂OH, -CHO or a C₁-C₆ alkyl acetal derivative, -COR² or a C₁-C₆ alkyl ketal derivative where R² is -(CH₂)_mCH₃ where m is 0-4 or COOR³ wherein R³ is a straight or branched C₁-C₃₀ alkyl group, a substituted or unsubstituted C₆-C₃₀ aromatic group, a substituted or unsubstituted C₃-C₃₀ cycloalkyl, a substituted or unsubstituted C₃-C₃₀ cycloalkylalkyl, a substituted or unsubstituted C₃-C₃₀ cycloalkenyl, a substituted or unsubstituted C₅-C₃₀ aryl, a substituted or unsubstituted C₅-C₃₀ arylalkyl, a substituted or unsubstituted C₅-C₃₀ heteroaryl, a substituted or unsubstituted C₃-C₃₀ heterocyclic ring, a substituted or unsubstituted C₄-C₃₀ heterocyclylalkyl, a substituted or unsubstituted C₆-C₃₀ heteroarylalkyl, the process comprising a Sonogashira coupling reaction between a compound of formula II wherein X and R have the aforestated meanings, with a compound of formula III X'-A-(CH₂)_n-B (III) wherein X' is a halogen and A, n and B have the aforestated meanings, in the presence of a base and a transition metal catalyst and in a polar aprotic solvent.