Scheme 1. Synthesis of an Advanced P2–P4 Macrocyclic Intermediate.
Reagents and conditions: (a) DSC, pyridine, DMAP, MeCN, 40 °C; (b) 2, Et3N, MeCN; (c) DIAD, Ph3P, THF; (d) 3, PdCl2(MeCN)2tBu3P·BF4, K2CO3, Bn2NH, MeCN, 75 °C; (e) TFA, CH2Cl2; (f) HATU, DIPEA, DMF; (g) 10% Pd–C, H2, MeOH, THF, 1 atm.