Синтез 2-аміноетилпохідних піразоло[4,3-c]піразолів

• Datum: 2024
• Hauptverfasser: Vydzhak, Roman N., Panchishin, Svitlana Yа.
• Format: Artikel
• Sprache: English
• Veröffentlicht: V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine 2024
• Schlagworte: піразоло[4,3-c]піразоли; алкілювання похідних піразолу; гетерилацетонітрили; відновлення ціанометильної групи
• Online Zugang: https://bioorganica.com.ua/index.php/journal/article/view/87
• Назва журналу: Ukrainica Bioorganica Acta

Preparative method for the preparation of 2-aminoethyl derivatives of pyrazolo[4,3-c]pyrazoles is presented. Alkylation of 1-alkyl-3-methyl-1,4-dihydropyrazolo[4,3-c]pyrazoles with 2-(2-bromomethyl)-1H-isoindole-1,3(2H)-dione and chloroacetonitrile was carried out. In all cases, mixtures of isomeric products of 1- and 2-alkylation with isomer ratios of 1 : 0.8 were obtained. The mixtures of isomers were separated by chromatography and the target compounds did not contain impurities of another isomer. All phthalimide derivatives of pyrazolo[4,3-c]pyrazoles were converted into the corresponding 2-heterylethylamines, which were isolated as dihydrochlorides. The reduction of the nitrile group of (4,6-dimethylpyrazolo[4,3-c]pyrazol-1(4H)-yl)acetonitrile and (4,6-dimethylpyrazolo[4,3-c]pyrazol-2(4H)-yl)acetonitrile under the action of various reagents was investigated: hydrogen at 20 atm on Raney nickel, lithium aluminum hydride in diethyl ether, and borane-dimethyl sulfide complex in tetrahydrofuran. The best results were obtained when reducing cyanomethyl derivatives with borane-dimethyl sulfide complex. In this case, the yields of the target amines are more than 90 percent. This is a preparative, convenient, and well-reproducible method and has been successfully applied to the synthesis of a number of 2-aminoethyl derivatives. The structure of the synthesized compounds was confirmed by 1H and 13C NMR spectroscopy. In vitro screening studies of antitumor activity were conducted on 60 cancer cell lines for the four synthesized compounds