A NEW METHOD FOR PREPARING 6-NITRO-2-(4-BOC-PIPERAZIN-1-YL)-3H-QUINAZOLIN-4-ONE

• Main Authors: A. Yu. Kornylov, A. A. Krysko, O. L. Krysko, S. E. Sambursky, S. A. Andronati
• Format: Article
• Language: English
• Published: Odessa I. I. Mechnikov National University 2017-11-01
• Series: Vìsnik Odesʹkogo Nacìonalʹnogo Unìversitetu: Hìmìâ
• Subjects: 2-аміно-3Н-хіназолін-4-они, паладієвий каталіз, C-N кросстикування
• Online Access: http://heraldchem.onu.edu.ua/article/view/115919

The 2-amino-3H-quinazolin-4-one scaffold is found in a large number of molecules with physiological significance and pharmaceutical utility. Previously we synthesized a series of potent antagonists of fibrinogen receptor, derivatives of 2-(piperazin-1-yl)-3H-quinazolin-4-one. The key building block for preparing the above series of compounds is 6-amino-2-(4-Boc-piperazin-1-yl)-3H-quinazolin-4-one, which was synthesized by hydrogenation of 6-nitro-2-(4-Boc-piperazin-1-yl)-3H-quinazolin-4-one. In turn, the nitro derivative was obtained starting from isatoic anhydride in four stages, by a method that can be considered classical, but difficult. The purpose of this work is to simplify the preparation of 6-nitro-2-(4-Boc-piperazin-1-yl)-3H-quinazolin-4-one. We proposed an effective method for the synthesis of 6-nitro-2-(4-Boc-piperazin-1-yl)-3H-quinazolin-4-one based on a sequential process, C-N cross-coupling and intramolecular amidation. As the arylhalogenide, 2-bromo-5-nitrobenzoic acid methyl ester was used, as the N-nucleophile, 4-Boc-piperazine-1-carboxamidine, a guanidine derivative, was used. In the study, we used two types of catalytic systems, which both gave good results. The application of the third generation of Palladacycleprecatalyst –[(4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene)-2-(2′-amino-1,1′-biphenyl)] palladium(II) methanesulfonate, leads to the production of the target product in a high yield, in comparison with the use of the catalytic system: precatalyst – Tris(dibenzylideneacetone) dipalladium(0) chloroform adduct and Buchwald Ligands – 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene. The structure of the title compound was confirmed by spectroscopy 1H and 13C NMR, and FAB mass spectrometry methods, purity was controlled by HPLC. This method has potential implications for the design of various 2-amino-3H-quinazolin-4-ones.