Scheme 2. Synthesis of compounds B01–B13. Reagents and conditions: (a) Pd2(dba)3, xantphos, Cs2CO3, dry DMF, Ar, 120 °C, 8 h, 65.9%; (b) bis(pinacolato)diboron, Pd(dppf)Cl2, Cs2CO3, dry dioxane, Ar, 100 °C, 4 h; (c) 2,5-difluorobenzyl bromide, Pd(PPh3)4, Cs2CO3, dioxane : H2O = 5 : 1, Ar, 80 °C, 4 h, 48.6%; (d) CF3COOH, 60 °C, 5 h; (e) NaOH, methanol : H2O = 3 : 1, 60 °C, 4 h, 65.7%; and (f) I) appropriate amine, PyBop, DIPEA, THF, 0 °C, 2 h and II) 4 N HCl/ethyl acetate, r.t., 4 h, 28.8–55.5%.
