“…Considerable experimentation was needed to optimize the yield of the macrolactamization to give 14a, and the important results are summarized in Table 1. An extensive screening was conducted of condensing agents, including the carbodiimide reagents N,N′-dicyclohexylcarbodiimide 15a (DCC; Table 1, entry 1) and 1 -ethyl-3-[3-(dimethylamino)propyl]carbodiimide monohydrochloride 15b (EDCI; entry 2); the benzotriazole-based uronium salt 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b] pyridinium 3oxide hexafluorophosphate 16 (HATU, entry 3); the imidazolium-type reagent 2-chloro-1,3-dimethylimidazolinium hexafluorophosphate 17 (CIP; entry 4); the pyridinium reagents 2-bromo-1-ethylpyridinium tetrafluoroborate 18a (BEP; entry 7) and 2-chloro-1-methylpyridinium iodide 18b (CMPI; entry 8); the phosphonium-based reagent (7-azabenzotriazol-1-yloxy)tris(pyrrolidino)phosphonium hexafluorophosphate 19 (PyAOP; entry 9); and the phosphonic acid derivatives pentafluorophenyl diphenylphosphinate 20 (FDPP; entry 5), 3-(diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one 21 (DEPBT; entry 6), and bis(2-oxo-3-oxazolidinyl)phosphinic chloride 22 (BOP-Cl; entry 10). The reactions (entries 1-10) were performed in highly dilute solutions in DMF for 24 hours.…”