Зручний підхід до синтезу заміщених 2-(метиламіно)хінолін-3-карбоксамідів

• Date: 2015
• Main Authors: Muzychka, L. V., Smolii, O. B., Biletskiy, I. I., Vasilenko, O. M.
• Format: Article
• Language: Ukrainian
• Published: National University of Pharmacy 2015
• Subjects: конденсація; піримідо[4; 5-b]хінолін-2; 4(1Н; 3Н)-діони; 5-деазаалоксазини; 2-(метиламіно)хінолін-3-карбоксаміди; УДК 547.831 547.859
• Online Access: https://ophcj.nuph.edu.ua/article/view/ophcj.15.855
• Journal Title: Journal of Organic and Pharmaceutical Chemistry

The paper is devoted to the synthesis of new 2-(methylamino)quinoline-3-carboxamide derivatives by the pyrimidine cycle hydrolytic cleavage of pyrimido[4,5-b]quinoline-2,4(1H,3H)-diones. These later were synthetized in high yields by interaction of available 1,3-dimethyl-6-piperidinyl-5-formyluracil with aromatic amines. The reactions with participation of ortho- and para-substituted aromatic amines proceed regioselectively to give 1,3-dimethylpyrimido[4,5-b] quinoline-2,4(1H,3H)-diones with substituents in positions 7 and 9 of the heterocycle. The use of metha-methoxyand metha-fluoroaniline leads to the mixture of 6- and 8-substituted 1,3-dimethylpyrimido[4,5-b]quinoline-2,4(1H,3H)- diones, which under basic conditions were cleaved into amides of quinoline-3-carboxylic acid. The mixture of 2-(methylamino)quinoline-3-carboxamides obtained was separated by column chromatography. Application of the correlation NMR spectroscopy method (NOESY, COSY, HSQC, HMBC) has allowed to reliably determine the structures of 1,3-dimethyl-5-formyluracil derivatives with aromatic amines condensation products. The amino-imino prototropic tautomerism occurs at 120°C. It facilitates syn-anti-isomerization promoted cyclization and leads to 1,3-dimethylpyrimido[4,5-b]quinoline-2,4(1H,3H)-dione. The structure of the compounds obtained has been proven using the methods of NMR 1 Н, 13C-spectroscopy, mass-spectra and elemental analysis.