Reagents and conditions: (a)
SOCl2, DMF, DCM, 0 °C; (b) 1,4-dimethoxybenzene, AlCl3, DCM, 0 °C, 55%; (c) BBr3, DCM, −78
to 0 °C, 57%; (d) DHP, PPTS, DCM, 70%; (e) 4-iodobenzaldehyde,
piperidine, DBU, s-butanol, reflux, 75%; (f) MeMgCl,
THF, 0 °C to rt, 98%; (g) 80% AcOH/water, 90 °C, 67%; (h)
DHP, PPTS, DCM, 55%; (i) ethane-1,2-diol, CuI, 1,10-phenantroline,
K2CO3, butyronitrile, 125 °C, 58%; (j)
methanesulfonyl chloride, TEA, DCM, 0 °C, 88%; (k) 17h,
17j–k: CuI, K2CO3, butyronitrile,
125–135 °C, 2–4 d, 75–82%; (l) 17c–g,
17i: K2CO3, acetonitrile, 60 °C
to reflux, 62–76%; (m) 80% AcOH/water, rt, 27–85%.