Scheme 2.

Synthesis of 7-trifluoroethoxy substituted THIQ derivatives 19a-c.^a

^aReagents and Conditions: (a) BrCH₂CO₂Et, iPr₂EtN, Bu₄NI, DMF, rt, 16 h; (b) 2N NaOH (aq), EtOH, rt, 16 h; (c) 3-aminomethylpyridine, HATU, iPr₂EtN, DMF, rt, 16 h; (d) CF₃CH₂I, Cs₂CO₃, DMF, 100 °C, 2 h; (e) 4-Hydroxy-3-methoxyphenylethylamine, HBTU, iPr₂EtN, DMF or DCC, HOBt, Et₃N, THF, rt, 16 h; (f) (i) POCl₃, CH₃CN, reflux, 1 h; (ii) NaBH₄, MeOH, 0 °C to rt, 16 h; (g) BrCH₂CONHCH₂Ph, iPr₂EtN, Bu₄NI, DMF, rt, 16 h; (h) CF₃CH₂I, Cs₂CO₃, DMF, 100 °C, 2 h.