The Sonogashira alkynylation of acid chlorides can be efficiently conducted in less than an hour by performing the reaction in tetrahydrofuran as a solvent and in the presence of one stoichiometrically necessary equivalent of triethylamine as a base. This approach also opens new avenues for consecutive one-pot multicomponent reactions. As an example, the one-pot three-component pyrimidine synthesis illustrates the versatility of this modified Sonogashira protocol as an entry to diversity-oriented heterocycle synthesis in a one-pot fashion. The protocol can be completed within a few hours.