Scheme 6. Synthesis of Compounds 13–15, 20, 21, 25, and 26^a.

^aReagents and conditions: (i) 2-oxobutyric acid, H₂SO₄, EtOH, reflux, 8 h, 58%; (ii) KOH, MeOH, reflux, 3 h; (iii) oxalyl chloride, DCM, rt, 1 h; (iv) NH₃·H₂O, rt, 2 h; (v) POCl₃, CHCl₃, reflux, 4 h, 56–96% (4 steps); (vi) LAH, THF, 0 °C to rt, 3 h, 80–97%; (vii) PCC, DCM, rt, 5 h, 78–86%; (viii) methyl azidoacetate, MeONa, MeOH, −15 to 4 °C, overnight 73–83%; (ix) TBDPSCl, imidazole, DCM, rt, 2 h; (x) NIS, TFA, CH₃CN, 50 °C, 12 h, 92% (2 steps); (xi) BuLi, DMF, THF, −78 to 0 °C, 2 h; (xii) MeI, Me₂CO, reflux, 2 h, 87% (2 steps); (xiii) (synthesis of 60a,c,d) xylene, reflux, 0.2 h, 50–81%; (xiv) KH, t-BuLi, DMF, THF, −90 to 0 °C, 2 h, 32–89%; (xv) (synthesis of 60b) Boc₂O, DMAP, CH₃CN, rt, 1 h, 96%; (xvi) 2.2 equiv of NBS, AIBN, CCl₄, reflux, 5 h; (xvii) Ag₂CO₃, Me₂CO/H₂O, rt, 24 h, 60% (2 steps); (xviii) TFA, DCM, rt, 1 h, 81%; (ix) 39, Et₃N, NaBH(OAc)₃, DCM, rt, overnight, 28–93%; (xx) 2-bromoacetamide, Cs₂CO₃, DMF, rt, 4 h, 25–37%; (xxi) BBr₃, DCM, rt, 24 h, 68%.