Heterocyclic Derivatives of 4-Amino-1,5-dimethyl-2-phenyl-1,2-dihydro-3 H- pyrazol-3-one
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rocyclic Derivatives of 4-Amino-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one E. A. Akishinaa, D. V. Kazaka, E. A. Dikusara,*, E. G. Zalesskayaa, N. A. Zhukovskayaa, S. G. Stepinb, and V. I. Potkina a Institute
of Physical Organic Chemistry, National Academy of Sciences of Belarus, Minsk, 220072 Belarus State Order of Peoples’ Friendship Medical University, Vitebsk, 210009 Belarus *e-mail: [email protected]
b Vitebsk
Received April 1, 2020; revised April 1, 2020; accepted April 9, 2020
Abstract—A convenient and scalable preparative method for the synthesis of azomethines from 4-amino-1,5dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one and substituted benzaldehydes, as well as 1,2-oxazole and 1,2-thiazolecarbaldehyde was developed. Keywords: azomethines, (iso)nicotinic acid, pyrazolone, 1,2-oxazoles, 1,2-thiazoles
DOI: 10.1134/S1070363220080095 A number of pyrazolone derivatives show analgesic, anti-inflammatory, antipyretic activity [1, 2]. Their use in medicine is decreasing due to the side effects of these compounds, as well as due to the appearance of more effective drugs [3]. The promising directions of the synthesis of new biologically active compounds of the pyrazolone series include the construction of azomethine heterocyclic derivatives from 4-amino-1,5-dimethyl-2-phenyl-1,2-
dihydro-3H-pyrazol-3-one 1 and aromatic or heterocyclic aldehydes [4–8]. We have developed a convenient and scalable method for the synthesis of (Z)-azomethines starting from 4-aminopyrazolone 1 and benzaldehydes substituted with methoxyl and ethoxyl groups, as well as nicotinoate and isonicotinoate fragments at various positions of the aromatic core (2–13), as well as from substituted isoxazole- and isothiazolecarbaldehydes (14 ‒16, Scheme 1).
Scheme 1.
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HETEROCYCLIC DERIVATIVES
Azomethines with alkoxyl and alkoxycarbonyl groups were obtained in preparative yields (75–85%) through condensation of 4-amino-1,5-dimethyl-2-phenyl-1,2dihydro-3H-pyrazol-3-one 1 with alkoxy(formyl)phenylpyridine-3(4)-carboxylates, 5-aryl-1,2-oxazoleand 4,5-dichloro-1,2-thiazole-3-carbaldehydes in anhydrous methanol under reflux. The reaction proceeded under mild conditions, which favored the retention of labile ester groups, and was completed in 1.5–2 h. Compounds 2–17 contain a number of pharmacophoric groups and can be potential drugs. They are capable of forming metal complexes with Zn, Cu, Ag, Pd, Pt, Ce, La, and other metals [9–11]. The presence of pyridine substituents at various positions of the benzene ring of compounds 2–13 makes it possible to study the effect of topology on their biological activity. The resulting compounds did not require further purification. Their purity was ~ 98–99%. The synthesized compounds are yellow or orange fine-crystalline substances; they can be used for testing for fungicidal and antimicrobial activity. Azomethine 12 was reduced under mild conditions using Na[BH(OAc)3] in benzene to form amine 17, while hydrolysis of the ester group and reduction of carbonyl moiety did not occur (Scheme 1). When
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