Scheme 4.
Convergent synthesis of constrained indazole-based 4EGI-1 mimetic via N-arylation of 1H-indazole-3-carboxylic acid by 2-halo-4-phenylthiazole. Reagents and conditions: i) KSCN (2 eq), acetonitrile, reflux, overnight; ii) HCl(g) or HBr (g), dry ether, 0 °C to rt, overnight; iii) HNO3/H2SO4 (conc.); iv) 1H-indazole-3-carboxylic acid or 5-nitro-1H-indazole-3-carboxylic acid, NaOH (2.2 eq) in DMSO, N2.