Scheme 2.

Synthesis of Nonbasic Warhead Series Compounds 16–24^a

^aR² is defined in Table 2. Conditions: (a) (1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)boronic acid, PdCl₂(dppf)·CH₂Cl₂, K₂CO₃, 1,4-dioxane/H₂O, 90 °C, overnight, 85%; (b) LiBHEt₃ (1 M THF), THF, 0 °C, 1 h, 95%; (c) PBr₃, CH₂Cl₂, 0 °C, 90%; (d) R²–azole, MeCN, 50 °C, overnight, 45–60%.