Derivatives of 1-(2-pyridyl)-4,5,6,7-tetrahydroindazole

Abstract

Derivatives of indazole and other pyrazole-containing condensed systems are attracting attention because of their biological activity and the possibilities of further conversions [1][2][3][4][5][6][7]. Therefore, continuing the work reported in [8][9][10][11][12][13][14], we have obtained a number of derivatives of 1-(2-pyridyl)-4,5,6,7-tetrahydroindazole.The oxidation of 1-(2-pyridyl)-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydroindazole by selenious acid, l:bllowing the procedure used in [9], gives the ~-diketone lb. In the IR spectrum of the 4,5-dioxo derivative lb, intense absorption bands of carbonyl groups are observed at 1725 and 1676 cm -1, and in the PMR spectrum a signal of protons of the C(7)-methylene group at 3.73 ppm. Oxidation of the diketone Ib with hydrogen peroxide in a mixture of formic acid and acetic anhydride, in accordance with [9, 15], gives the dicarboxylic acid II. Boiling of the acid II with acetic anhydride leads to the formation of an anhydride -the oxepinopyrazole III, the structure of which is confirmed specifically by the presence of characteristic IR absorption bands of anhydrides at 1777 and 1730 cm -1, and also the corresponding signals of protons in the PMR spectrum (corresponding in number and character).In reactions of the 4,5-dioxo derivative Ib with hydrazides of nicotinic, isonicotinic, salicylic, and 3-bromobenzoic acids, the corresponding 4-oxo-5-acylhydrazonoindazoles IVa-d are obtained; their PMR spectra exhibit downfield signals of NH protons involved in an H-chelate ring (6NH 14.33-14.61 ppm).We also obtained the tosylhydrazone IVe, which, when subjected to the action of alkali, is converted to the 4-oxo-5-diazo derivative Ic. Bromination of the indazole Ia by N-bromosuccininlide (NBS) affords the 7-bromo derivative Va, even with excess of the brominating agent; but bromination of Ia by pyridinium bromide-perbromide (PBP), depending on the mole ratio of reagents, gives the 4-oxo-5-bromo derivative (Id) and the 4-oxo-5,5-dibromo derivative (Ie), respectively. This is consistent with the relationships in the bromination of 4-oxo-4,5,6,7-tetrahydroindazoles that were noted in [9, 11]. The 5,7-dibromo derivative Vb was obtained by the action of PBP on the 7-bromoindazole Va. The 4,5-dioxo-7-bromoindazole Vc was obtained from the 4,5-dioxoindazole Ib by the action of either N-bromosuccinimide or pyridinium bromide-perbromide, which is observed for the first time in the 6,6-dimethyl-4,5,6,7-tetrahydroindazole series.As a result of the introduction of a bulky substituent -bromine -into position 5 or 7, the C(6)-methyl groups become magnetically nonequivalent and are observed in the PMR spectrum, in contrast to 5,7-unsubstituted 6,6-dimethyl~,5,6,7-tetrahydroindazoles and their 5-oxo (Ib), 5-diazo (Id), and 5-hydrazono (IV) derivatives, in the form of two signals. The signal of the remaining C(7 ) proton in compounds Va-c undergoes a considerable downfield shift to 6.36 ppm (Va), 6.53 ppm (Vb), and 6.58 ppm (Vc).

Reactions of 1-aryl- and 2,3-diaryl- 5-diazo-6,6-dimethyl-4-oxo-4,5,6,7-tetra- hydroindazoles with N-ethyl- and N-phenyl-substituted maleimides

“…1 Riga Technical University, Riga LV-1048, Latvia. 2 In the development of the work mentioned above the reaction of compounds 1a-c and 2a-c [26,27] with N-ethyl-(3a) and N-phenylmaleimide (3b) is described in the present report. This was carried out according to classical procedures [28,29] and permitted the synthesis in high yield of the corresponding 6,6-dimethyl-4,4',6'-trioxo-4,5,6,7,3',3'a,4',5',6',6'a,-decahydrospiro [ndazole-5,3'-pyrrolo [3,4-c]pyrazoles] 4a-f, 5a-d.…”

5-Diazo-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydroindazoles in [3+2] cycloaddition reactions

“…Among them agonists of estrogen receptors [1] and dopamine D3 receptors [2], HIV protease inhibitors [3], and new anti-inflammatory substances [4] have been discovered. In this connection in a continuation of researches on the synthesis of 4,5-bifunctional 6,7-dihydro-and 4,5,6,7-tetrahydroindazoles [5-10] we realized [3+2] cycloaddition reactions between 5-diazo-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydroindazoles 1a-d and maleic anhydride.The diazoindazoles 1a,b,d were obtained by the decomposition of the corresponding tosylhydrazones 2a,b,d in a water-ethanol solution of sodium hydroxide according to the procedure in [11,12] that we used earlier for the preparation of the diazoindazoles 1c and 3. …”

“…The diazoindazoles 1a,b,d were obtained by the decomposition of the corresponding tosylhydrazones 2a,b,d in a water-ethanol solution of sodium hydroxide according to the procedure in [11,12] that we used earlier for the preparation of the diazoindazoles 1c and 3.…”