Synthesis and Reactivity of (Z)-3-Benzoylamino-4-dimethylamino-2-oxo-3-butene. Preparation of 1-Aryl- and 1-Heteroaryl-substituted 4-Benzoyl-amino-5-methyl-1H-pyrazoles

Z)-3-Benzoylamino-4-dimethylamino-2-oxo-3-butene (4), prepared from 1-benzoylamino-2-propanone (3) and N,N-dimethylformamide dimethyl acetal, was converted regioselectively by reaction with a series of hydrazines (5) into 1-substituted 4-benzoylamino-5-methyl-1H-pyrazoles (8).Reactions of 4 with primary amines (10) and with dimethylbarbituric acid (12) afforded the dimethylamine substitution products (11) and (13), respectively.Treatment of the butenone (13) with ammonia furnished tetrahydropyrido [2,3d]pyrimidine derivative (14).2][3] Pyrazoles and their derivatives found a widespread use in various applications in last decades.0][11][12][13][14] The standard method of synthesis of pyrazoles consists in the condensation of 1,3-bifunctional compound with hydrazine or its derivatives, and 1,3-dipolar cycloadditions.1b,5,15,16 The 4-nitrogen substituted 2-pyrazolin-5-ones are usually prepared by modification of already formed pyrazolinones, 17 while the 5-substituted 4-amino-3-hydroxypyrazoles have been synthesized by transformation of β-keto esters, via oxime formation, into 2-amino-β-keto esters followed by treatment with hydrazines 18 and from methyl 2-benzoylamino-3-oxobutanoate and hydrazines. 19Recently, pyrazolidinones have been used for regio-and stereoselective synthesis of rel-(2R,3R)-3-alkylamino-3phenylalanine amides 20 and alanine esters, 21,22 tetracyclic systems, 23 rel-(4'R,5'S)-3-(5-aryl-3,4-bis(hydrazinocarbonyl)-4,5-dihydro-1H-pyrazol-1-yl)-3-methylbutanohydrazides, 24 and (1Z)-1-arylmethylidene-5,5-dimethyl-3-oxopyrazolidin-1-ium-2-ide azomethine imines. 25[31][32][33][34] In this paper we present the synthesis and transformations of (Z)-3-benzoylamino-4-dimethylamino-2oxo-3-butene (4), prepared in 3 steps from hippuric acid (1).This was first treated with N,N-dimethylacetamide and POCl 3 to give the oxazolone (2), which was then transformed into 1-benzoylamino-2propanone (3) by treatment with a mixture of methanol and hydrochloric acid.Heating of 3 with N,Ndimethylformamide dimethyl acetal (DMFDMA) in dry toluene for 45 min afforded (Z)-3-benzoylamino-4-dimethylamino-2-oxo-3-butene (4) in 58% overall yield.In order to study the reactivity of compound (4) a series of hydrazines (5a-l) were selected.Since 4 contains two functional groups, the carbonyl and the enamino groups, which react easily with hydrazines, two intermediates can be formed: a) the enehydrazine (6) by substitution of the dimethylamino group and b) the corresponding hydrazone ( 7) by the reaction with the carbonyl group.From these two intermediates two isomeric pyrazole derivatives, either 1-substituted 4-benzoylamino-5-methyl-1H-pyrazole (8) or 1-substituted 4-benzoylamino-3-methyl-1Hpyrazole (9) could be formed by cyclization.The isolation of intermediate was not possible, since further cyclization occurs at room temperature to give pyrazole derivatives (Scheme 1).The X-Ray structure of the product derived from 2-hydrazinopyrimidine (5j) was determined showing that compound is 4-benzoylamino-5-methyl-1-(pyrimidin-2-yl)-1H-pyrazole (8j) (Figure 1). Figure 1.Ortep view at the 50% probability level for compound (8j) showing the labeling of the non-hydrogen atoms.H atoms are drawn as circles of arbitrary radii.