Objective To synthesize four related substances:1b,1c,1d,and 1e according to the synthetic process of aprepi-tant and its quality standard of USP and EP. Methods The impurities 1b,1c,and 1d were synthesized from 3,5-bis(trifluoromethyl) acetophenone through asymmetrical catalytic reduction reaction,condensation reaction,Grignard reaction ,catalytic hydrogenation and substitution. The impurity 1e was synthesized from(R)-α-methylbenzylamine through 7 reaction steps including esterification,reduc-tion,condensation ect. Results All the four related substances were confirmed by LC-MS and NMR. The results indicated that purity of the product surpassed 95%through HPLC. Conclusion These related substances can be taken as the references for the quality con-trol of aprepitant.