Synthesis of some potential biologically active quinazolyl, quinolyl, isoquinolinyl and indazolyl derivatives containing alfa-hydroxy carboxylic acid moieties as substituents

Abstract

Chapter 1: General introduction: This chapter deals with the introductory aspects of -hydroxy carboxylic acids, quinazolinones, quinolines, isoquinolinones and indazoles, their importance, synthesis and chemical properties. Chapter-2: Section A: STUDIES ON SYNTHESIS OF -HYDROXY CARBOXYLIC ACIDS To a solution of optically pure L-amino acids (34a-f) in 6% H2SO4 and acetone (1:1 ratio), were added 3 molar equivalents of sodium nitrite in water solution at 0°C to furnish -hydroxy carboxylic acids (35a-f) in good yields. (Scheme 2.1) Scheme 2.1: R NH2 O OH R OHO OH 34a-f 35a-f Reaction conditions: H2SO4/NaNO2/ H2O/Acetone/ (-) 50C-RT Chapter-2: Section-B Synthesis of 3-aryl-2 quinazolinyl-phenylacetic acid ester derivatives The Section describes the design and synthesis of novel quinazolinone derivatives like 2-(2-(4-((3,4-dihydro 4-oxo-3- arylquinazolin-2-yl)methyl) piperazin-1-yl)acetoyloxy)-2-phenyl acetic acid esters (57) incorporating three biologically active moieties such as quinazolinone, piperazine and (2S)-2-hydroxy-2-phenylacetic acid derivatives in a single molecule. Reaction of 58 with 59 in presence of K2CO3 and KI, gave the title compound, 2-(2 (4-((3,4-dihydro-4-oxo-3-arylquinazolin-2-yl)methyl) piperaz -in-1-yl)acetoyloxy)-2 phenyl acetic acid esters (57). The structures of all the new compounds obtained in the present work are supported by spectral and analytical data. (Scheme 2.24) Scheme-2.24 O O OR ON N N NO Ar O O OR OCl N HN N NO Ar + 58 59 57 i Reagents and Conditions: i) K2CO3, KI, CH3CN, Δ. The reaction of 2-(chloromethyl)-3-(2-methylphenyl)-3,4-dihydro-4- quinazolinone 62c (22) (i.e.66c, Ar= C6H4-OCH3-3) with 4- Piperidone/morpholine/4-ethyl piperidinecarboxylate, K2CO3 and KI, under refluxing acetonitrile for 90-120 min. resulted in the formation of 64/65/66. (Scheme 2.25)