Palladium mediated synthesis of isoquinolinone derivatives and study of their biological activities

Abstract

Isoquinolinones (I-oxo-l ,2-dihydroisoquinoline) are a class of fused heterocycles that are of increasing interest in synthetic and pharmaceutical chemistry. A convenient and facile method for the synthesis of 1,2,3,4-tetrahydro-l-oxoisoquinoline-3-carboxylic acid by. palladium-catalyzed reaction of N-substituted-2-iodobenzamide with acrylic ester IS reported. N-(Alky) Aryl-2-iodobenzamides 10-15, when stirred with acrylate 16-21 111 presence ofbis (triphenyl phosphine) palladium (II) chloride in DMF and triethylamine at 80 °C for 24 h gave N-substituted-3-alkylisoindolin- I-one acetate 22-29 which af1()rded N-substituted-l,2,3,4-tetrahydro-l-oxoisoquinoline-3-carboxylic acid 30-35 on base/acid catalyst hydrolysis. ~I C_NHR II 10 - 15 0 2 / H,C = CHCN ~ ~ - 20 CH2-COORI H,C = (: - CORI / H,C = CHCHO ~ 16-19 21 (PPhJ),PdCI2, E-tJN •. N-R + 0 rQl NHR DMF, N, aIm I ~ 80 °c, 24 hrs. 22 _ 29 0 36.-d 0 . rArJCOOH 0yN-R o 30 - 35 (i) NaOH (1.5 eq), MeOH Reflux 1.5 - 2 hrs. or (ii) 2N H2S04, 80 "C, 1.5 - 21m. In Vitro antimicrobial activity of 3-substituted isoindolinone acetate and isoquinolinone- 3-carboxylic acid were evaluated. The compounds demonstrated mild growth inhihilion against antibiotic-susceptihle standard and clinically isolated strains or Gram positive and Gram-negative bacteria as well as human fungal pathogens.