4-Substituted 5-nitroisoquinolin-1-ones from intramolecular Pd-catalysed reaction of N-(2-alkenyl)-2-halo-3-nitrobenzamides

摘要: Abstract 4-Methyl- and 4-benzyl-5-aminoisoquinolin-1-ones are close analogues of the water-soluble PARP-1 inhibitor 5-AIQ. Their synthesis was approached through Pd-catalysed cyclisations N-(2-alkenyl)-2-iodo-3-nitrobenzamides. Reaction N,N-diallyl-2-iodo-3-nitrobenzamide with Pd(PPh3)4 gave a mixture 2-allyl-4-methyl-5-nitroisoquinolin-1-one 2-allyl-4-methylene-5-nitro-3,4-dihydroisoquinolin-1-one. N-Benzhydryl-N-cinnamyl-2-iodo-3-nitrobenzamide similarly 2-benzhydryl-4-benzyl-5-nitroisoquinolin-1-one 2-benzhydryl-4-benzylidene-5-nitro-3,4-dihydroisoquinolin-1-one. The isomeric products not interconvertible. A deuterium-labelling study indicated that isomers were formed by different pathways: π-allyl-Pd route classical Heck route. corresponding secondary amides N-allyl-2-iodo-3-nitrobenzamide N-((substituted)-cinnamyl)-2-iodo-3-nitrobenzamide good yields required 4-methyl- 4-((substituted)-benzyl)-5-nitroisoquinolin-1-ones, respectively, under optimised conditions (Pd(PPh3)4, Et3N, Bu4NCl, 150 °C, rapid heating). Hydrogenation nitro groups 4-benzyl-5-aminoisoquinolin-1-ones, which potent inhibitors activity.