Scheme 3

Synthesis of ERW1041E. Reagents and conditions: (i) hydroxylamine hydrochloride, H₂O, 2 h, room temperature (rt), then NaHCO₃, Br₂, 16 h, 0 °C to rt, 52%; (ii) allylamine hydrochloride, KHCO₃, H₂O, 3 h, rt, 50%; (iii) LiBH₄, ethanol/THF, 2 h, − 80 °C, then CDI, MeCN, 2 h, rt, 78%; (iv) proline methyl ester hydrochloride, DiPEA, DCM/DMF, 16 h, rt, 60%; (v) NaOH, dioxane/MeOH/H₂O, 2 h, rt, 89%; (vi) amine 4, EDC, HOBt, N-methylmorpholine, DMF, 2 h, rt, 96%