A serie of six new alkyne-2-chloroquinoline were synthesized in moderate yields (40-65%) via the Passerini three-component reaction (P-3CR) under mild green conditions. The P-3CR take place when a carboxylic acid, an oxo compound (aldehydes or ketones) and an isocyanide reacted to give α-acyloxy carboxamides. Recently it has been reported that small molecules containing alkynes promote interactions with different proteins in cells facilitating the detection or identification of protein targets.