Thieno[2,3-c]isoquinolin-5(4H)-one is known for its potential as an anti-ischemic agent through inhibition of poly(ADP-ribose) polymerase 1 (PARP1). However, the compound also inhibits many other enzymes of the PARP family potentially limiting its usability. The broad inhibition profile on the other hand indicates that this molecule backbone could be potentially used as a scaffold for development of specific inhibitors for certain PARP enzymes. These efforts call for novel synthetic strategies for substituted thieno[2,3-c]isoquinolin-5(4H)-one that could provide the needed selectivity. In this paper, an efficient synthetic strategy for 8-alkoxythieno[2,3-c]isoquinolin-5(4H)-ones through eight steps is presented and tested other synthetic pathways are discussed in detail. Synthesis of 7-methoxythieno[2,3-c]isoquinolin-5(4H)-one is also demonstrated to show that the strategy can be applied widely in the syntheses of substituted alkoxythieno[2,3-c]isoquinolin-5(4H)-ones.