Alternative amide coupling conditions were explored for the synthesis of acyclic bamidomethyl-vinyl sulfone 1 that would avoid the formation of cyclic byproduct 2 and the subsequent preparative HPLC separation (Table ). The original conditions using HBTU as the coupling agent and DIPEA as the base in DMF yielded a 60:40 mixture of 1 and 2 by analytical UPLC analysis (entry 1, Table ). Switching the coupling agent to hexafluorophosphate azabenzotriazole tetramethyl uronium (HATU) or benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP) resulted in a similar ratio of 1 and 2 (entries 2 and