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. Author manuscript; available in PMC: 2022 Apr 22.
Published in final edited form as: J Med Chem. 2021 Mar 31;64(8):5099–5122. doi: 10.1021/acs.jmedchem.1c00164

Scheme 4. (A) Synthesis of Naphthalene-Containing Isoxazole Derivative 32a.

Scheme 4.

aReagents and conditions: (a) (3-(4-bromophenyl)isoxazol-5-yl)methanol, Pd(PPh3)4, K2CO3, DMF, μW, 100 °C, 1.5 h, and 50% and (b) KOH, MeOH/H2O = 2:1, 50 °C, and 98%. (B) Synthesis of amide-containing isoxazole derivative 33. Reagents and conditions: (a) SOCl2, MeOH, rt, 15 h, and 98%; (b) 4-(trifluoromethyl)benzoic acid, HATU, DIPEA, DMF, rt, 5 h, and 70%; (c) B2pin2, PdCl2(dppf), KOAc, dioxane, 70 °C, 6 h, and 65%; (d) (3-(4-bromophenyl)isoxazol-5-yl)methanol, Pd(PPh3)4, K2CO3, DMF, 85 °C, 5 h, and 45%; and (e) KOH, MeOH, H2O, 50 °C, 3 h, and 62%.