Dobrydnev A. Synthesis of 5-amino-3(2H)-pyrrolinones and 5-amino-3(2H)-thiophenones based on a-functionalized carboxylic acids

The thesis is devoted to the synthesis of 5-amino-3(2H)-pyrrolinones and 5-amino-3(2H)-thiophenones with heterocyclic substituent at 4th position. The synthetic route based on interaction of hetaryl- and hetarylidenacetonitriles with N- and S-protected carboxylic acids chlorides. The elaboration of the acylated nitriles into the target aminopyrrolinones and aminothiophenones was achieved by saponification of the protecting group. The subsequent intramolecular addition of the primary amino or mercapto group in the intermediate to the nitrile group followed by consequent pyrrolinone or thiophenone ring formation ?-Aminoisobutanoic acid and some representatives of cyclic a-amino acids were converted to corresponding N-trifluoroacylated acid chlorides. The reaction of hetarylacetonitriles with above-mentioned acid chlorides gave the desired (3-cyano-2-oxo-3-hetarylpropyl)-2,2,2-trifluoroacetamides that upon detrifluoroacetylation provided the target 2-amino-3-hetarylpyrrolin-4-ones. The intereaction of hetarylidenacetonitriles with N-trifluoroacylated acid chlorides gave the desired (3-cyano-2-oxo-3-hetarylpropyl)-2,2,2-trifluoroacetamides that upon detrifluoroacetylation provided the target 2-(5-amino-2,3-dihydro-3-oxopyrrol-4-yl)-1,3-dialkylbenzimidazolium chlorides. Acylation of hetaryl- and hetarylideneacetonitriles with acetylmercaptoacetyl chloride gave 3-cyano-3-hetarylylidene-2-oxopropyl ethanethioates. 2-Amino-3-hetaryl-4(5H)oxothiophenes or 2-hetarylidene-3-oxo-4-sulfanylbutanenitriles were obtained on treating them with bases. Acylation of hetarylacetonitriles with 3-acetylmercaptopropionyl chloride gave 4-cyano-4-hetaryllidene-3-oxobutyl ethanethioates, deacetylation of which gave 2-hetarylylidene-3-oxo-5-sulfanyl-pentanenitriles.