Scheme 2.

Synthesis of analogs of the initial hit 3a with modifications to the ester and amide functional groups. (A) Synthesis of compound 5 by coupling intermediate 4 with 3-chloro-4-methoxyaniline. (B) Synthesis of compound 7 by coupling compoud 6 with 1. Reagents and conditions: (a) CH₂Cl₂, oxalyl chloride, DMF (cat), rt, 2 h; (b) CH₂Cl₂, glycine, Et₃N, rt, 2 h; (c) CH₂Cl₂, 3-chloro-4-methoxyaniline, Et₃N, rt, 2 h; (d) DMF, ethylene carbonate, molecular sieve 4 Å (cat), 150°C, 4 d; (e) CH₂Cl₂, 1, EDC, DMAP (cat), rt, 4 h.