The invention discloses a synthesis method of 2-substituted-3, 4-dihyidro-1-isoquinoline ketone compound and a relative application in the drug preparation for cardiovascular disease, wherein the compound is represented as above, R1 is gaseous normal alkyl and aromatic group or various substituted alkyl and aromatic group of C1-C19, R2 is OH, OCH3, CH3, NO2 and halogen or the like and can be one or more substituents. The preparation of 2-substituted-3, 4-dihyidro-1-isoquinoline ketone compound uses isovanillic acid ester as raw material, via six-step reaction as allyl etherified, Claisen rearrangement, oxidation, reaction with primary amine (generating Schiff base), reduction and aminolysis of molecular lactone, to synthesize the product. The isolated arterial ring tension test proves that the compound can relax vessel effectively. The 2-substituted-3, 4-dihyidro-1-isoquinoline ketone compound is a new potential cardiovascular drug, with wide application for preparing the drug of cardiovascular disease.