Scheme 1.

Synthesis of the Substituted Benzamide Series Compounds 2 – 13^a

^aR¹ is defined in Table 1. Conditions: (a) B₂Pin₂, KOAc, Pd(dppf)Cl₂, 1,4-dioxane, 85 °C overnight, quant.; (b) 2-bromo-5-fluorotoluene, Pd(dppf)Cl₂, K₂CO₃, 1,4-dioxane:H₂O (3:1), 95 °C, 2 h, 68%; (c) 2 M LiOH, THF, rt, overnight, 94%; (d) R¹-benzyl amine, TBTU, i-Pr₂NEt, DMF, rt, 8 h, 37 – 84%; (e) PBr₃, CH₂Cl₂, rt, 2 h; (f) 1-methyl-2-aminoimidazole, i-Pr₂NEt, KI, MeCN, 80 °C, 4 h, 7 – 40%, over two steps.