Pyrazolo[5,4-h]quinazolines

Abstract

Keywords: 3,8-substituted 1-methyl-4,5-dihydropyrazolo [5,4-h]quinazolines, 1-(2-pyridyl)-and l-phenyl-4-chloro-5-formyl-3-methyl-6,7-dihydroindazoles.We continue work [1][2][3][4] describing the synthetic uses of l-phenyl-(1) and l-(2-pyridyl)-(2) 4-chloro-5-formyl-3-methyl-6,7-dihydroindazoles in their reaction with a series of amidines and their cyclic analogs (2-aminobenzimidazole and 5-aminotetrazole). In addition to C-carbamidines 2-carbamidino-5-trifluoromethylpyridine and 2-carbamidinopyrazinc, N-carbamidines carbamidinopyrrolidinc, 4-carbamidinomorpholine, and creatine were also used. In all cases, the single reaction products were the 3,8-substituted 1-methyl-4,5-dihydropyrazolo[5,4-h]quinazolincs (3)(4)(5)(6)(7)(8)(9).Reaction of chlorovinylaldehydes 1 and 2 with salts of carbamidinopyrrolidine and morpholine was carried out with prolonged (10-I 5 h) refluxing in absolute ethanol in the presence of two equivalents of KOH or, in the case of creatine hydrate, two hour refluxing in the presence of an equimolar amount of KOH. The reaction with 2-carbamidino-5-trifluoromethylpyridine and 2-carbamidinopyrazine salts also needed prolonged heating. In the first example it was best to use an equimolar amount of alcoholate and in the second KOH.The reaction with the tree bases of cyclic amidine analogs (5-aminotetrazole and 2-aminobenzimidazole)" was also carried out in the presence of an equimolar amount of alcoholate. Moreover, for the reaction of phenylindazole 1 with 5-aminotetrazole, the single reaction product is tetrazolo [l,5-a]pyrazolo [5,4-h] quinazoline10 and with 2-aminobenzimidazole benzimidazolo[l,2-a]pyrazolo[5,4-h]quinazoline 11. Treatment of l-(2-pyridyt)indazole 2 with 2-aminobenzimidazole leads to formation of both compound 12 and 5-aminomethyleneindazole 13. In contrast, the reaction of enol ether 14 (prepared from the chloro derivative 2 and sodium ethylate) with 2-aminobenzimidazole gave only compound 12.IR and ~H NMR spectroscopic data are fully in agreement with the proposed structures. Hence the JH NMR spectra confirm the presence in compound 13 ofa trans orientated aminomethylene group, identified by the doublet signals at 7.67 ppm (J = 13 Hz) for CH and at 11.34 ppm for NH (J = 13 Hz), together with the signal for the NH proton of the imidazole fragment at 11.56 ppm. In the IR spectrum, the NH bond frequency is seen in the range 3200-3050 cm t. In the spectra of compounds 3-12 no NH bonds were observed but for compound 9 the presence of the carboxylic hydroxyl function was established by vcoo. at 2650-2450 cm t and 8cc~orl at 10.5 ppm.

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

“…In the indazole derivatives 4 the methyl groups at C (6) and also each of the hydrogens of the C (7) methylene group appear as separate signals. In compounds 5 there are six-proton singlets for the two C (6) methyl groups and also singlets for the C (7) methylene groups.…”

“…The reaction of the diazoindazoles 1b,c and 3a,b [12] with dimethyl acetylenedicarboxylate is carried out by keeping equimolar amounts of the reagents in methylene chloride at 20°C for 4-5 days. In all cases the corresponding 1',3'-or 2',3'-substituted 4,5-di(methoxycarbonyl)-6,6'-dimethyl-4'-oxo-4',5',6',7'-tetrahydro-3H-spiropyrazole-3,5'-indazoles 6c,d and 7a,b were obtained.…”

“…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.…”

“…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.…”