Scheme 5. General Synthetic Routes for Third-Generation Compounds.

Reagents and conditions: (a) MsCl, TEA, DCM, rt, 3 h; (b) 2d, K₂CO₃, DMF, 70 °C, overnight; (c) K₂CO₃, DMF, 70 °C, overnight; (d) HCl 1 N, THF (1:1), 50 °C, 2 h; (e) 1c,d, NaBH(OAc)₃, TEA, DMF, rt, overnight; (f) Na₂HPO₄, NaClO₂, 2-methyl-2-butene, t-BuOH, H₂O, rt, 4 h ; (g) 1e,f, HATU, HOAt, DIPEA, DMF, rt, 2 h.