Scheme 1.

(A): Synthesis of macrocyclic inhibitors 7–23 and 41–63 according to Lücking et al.^30a (B): Back-pocket targeting moieties of derivatives 7–20. (C): Synthesis of borpinacole esters 36–40.^b

^aReagents and conditions: (a) N-Boc-1,3-diaminopropane, triethylamine, acetonitrile, rt, 3 h; (b) 4 N HCl in 1,4-dioxane, acetonitrile, rt, 3 h; (c) triethylamine, acetone/water (3:1), rt, 5 h; (d) iron, ammonium chloride, methanol/water (9:1), reflux, 3 h; (e) 4 N HCl in 1,4-dioxane, acetonitrile, water, 2-butanol, reflux, 6 h; (f) potassium carbonate, [1,1’-Bis(diphenylphosphino)-ferrocene]palladium(II) dichloride, boronic acid, 1,4-dioxane/dimethylformamide (1:1), 100 °C, μW, 2 h. ^bReagents and conditions: (a) 2-bromopropane (for 31) or iodomethane (for 32), cesium carbonate, dimethylformamide, rt, 16 h; (b) bis(pinacolato)diboron, [1,1’-Bis(diphenyl-phosphino)ferrocene]palladium(II) dichloride, potassium acetate, 1,4-dioxane, 100 °C, μW, 2 h.