Reactions of 3-methyl-1-(2-pyridyl)-4-chloro-5-formyl-6,7-dihydroindazole

Abstract

Earlier we modified indazoles in the reactions of 3-methyl-l-(2-pyridyl)-5-formyl-4-chloro-6,7-dihydroindazoles (I, II) with hydrazines, o-phenylenediamine, and certain C-nucleophiles [1]. In the present paper we discuss the reactions of the 3-chloroaldehydes (I-III) with guanidine, amidines, and hydroxylamine, leading to pyrazolo [5,4-h]quinazolines (IV-XII) and isoxazolo [5,4-e]indazole (XVII) respectively.When the chloroaldehydes (I, II) were boiled with guanidine carbonate, benzamidine hydrochloride, and 3-and 4-pyridinecarbamidine hydrochlorides in ethanol in the presence of sodium ethoxide, the corresponding 8-substituted 1-methyl-3-(2-pyridyl)-4,5-dihydropyrazolo[5,4-h]quinazolines (IV-IX) were obtained. 3-Methyl-l-phenyl-5-formyl-4-chloro-6,7-dihydroindazole (III) also reacts with 3-and 4-pyridinecarbamidines [2].The structure of the pyrazolo[4,5-d]quinazolines (IV-XII) is confirmed by the IR and PMR spectra (Table 1). Thus, the primary amino group of compound (IV) is characterized by the stretching vibrations at 3350 and 3150 cm -1, while the PMR spectrum contains a two-proton signal at t5 5.52 pprn.The reactions of the chloroaldehydes (I, II) with hydroxylamine hydrochloride in pyridine lead to the oximes (XIII, XIV). When boiled with acetic anhydride the chloroaldehydes (I, III) form the 4-acetoxy derivatives (XV) and (XVI). In the IR spectra of the enol acetates (XV) and (XVI) the carbonyl groups are characterized by absorption at 1774 (XV) and 1764 (XVI) cm -1. The treatment of 4-acetoxy-5-formylindazole (XV) with hydroxylamine leads to the isoxazolo[5,4-e]indazole (XVII).The aldoxime (XIII) is easily dehydrated to 3-methyl-l-(2-pyridyl)-4-chloro-5-cyano-6,7-dihydroindazole (XVIII) by boiling in acetic anhydride. Nucleophilic substitution of the chlorine atom in the latter is realized by the action of sodium alkoxide and also of potassium hydroxide and leads to the formation of the 4-ethoxy derivative (XIX) and 3-methyl-4-oxo-l-(2-pyridyl)-5-cyano-4,5,6,7-tetrahydroindazole (XX) respectively. The strong absorption band of the carbonyl group in the latter is found at 1686 cm -l, while vc__-N is formed at 2250 cm -1. The cyano ketone (XX) was also obtained by the action of hydroxylamine on 4-acetoxy-5-formylindazole (XV) in pyridine.

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][6][7][8][9][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.…”