Scheme 1.

Synthesis of Substituted Naphthalene Core Intermediates 13a-d^a

^aReagents and conditions: (a) CH₂Cl₂, fuming HNO₃, rt, 5 min, 51–62%; (b) CH₂Cl₂, triethylamine (TEA), Tf₂O, 0 °C → rt, 18 h, 66–85%; (c) toluene, 3-cyanoaniline, PPh₃, Pd(PPh₃)₄, K₂CO₃, 110 °C, 16 h, 66–85%; (d) tetrahydrofuran (THF)-MeOH (2:1), Pd–C, H₂, rt, 4 h, 62–93%; (e) acetic acid, bromine, rt, 1 h, 77%; (f) THF, ethyl chloromalonate, TEA, 0 °C → rt, 3 h, 70% (12a); (g) toluene-N,N-dimethylformamide (DMF) (9:1), monomethyl malonate, N,N′-dicyclohexylcarbodiimide (DCC), rt, 3 h, KO-t-Bu, rt, 3 h, 52% (11a → 13a); (h) toluene, malonyl chloride, 0 °C → rt, 80 °C, 20 min, 110 °C, 10 min, 40–68%; (i) THF, KO-t-Bu, rt, 3 h, quant. yield (12a → 13a); (j) acetic acid, bromine, 50 °C, 7 h, 81%; (k) DMF, N-bromosuccinimide (NBS), 50 °C, 5 h, 81%.