A cobalt-catalysed, ortho-directed, C-H activation of 8-aminoquinoline amides for the preparation of functionalised isoquinolones is reported. The C-H activation was performed with the amide derived from 8-aminoquinoline which acts as a bidentate directing group to facilitate the C-H activation at the ortho carbon atom of the amide towards annulation/cyclisation, with unsymmetrical 1,3-diynes. The work presented here is an exploration of the regiochemical outcome of an efficient and a novel route of synthesis that tries to gain a deeper insight into the regioselective preference for C-H activated annulations that result in the formation of a diverse range of alkynylated regioisomeric heterocycles. Of the four possible regioisomers, only one is formed as the major product depending on the stereoelectronic properties of the diyne in combination with the nature of the 8-aminoquinoline amide.