A convenient route for the synthesis of some new bi- and triheterocondensed uracils

Abstract

Some bifunctional heterocyclic systems having vicinal chlorocyano, chloroacetyl, and chloroethoxycarbonyl groups in their structures reacted with 6-amino-1,3-dimethyluracil to afford novel triheterocyclic systems having a pyrimidinedione moiety. Enaminones and α-cyanocinnamic acid derivatives in this reaction gave pyrido [2,3-d]pyrimidinediones. The antimicrobial activity of some new synthesized triheterocyclic systems was studied.Several bi-and oligocycles containing uracil rings were found to be an important class of compounds exhibiting biological and pharmacological activities. These compounds showed antitumor [1, 2], cardiotonic [3,4], antifungal [5,6], antibronchitic [7], antibacterial [6], and antifolate [8] activities. There are ample precedents for the synthesis of these fused heterocycles [9][10][11][12][13][14]. Most of these methods usually require rigorous conditions [15], long reaction times [16,17], and complex synthetic pathways [2]. As a part of our studies on diazines [18][19][20][21][22], the present investigation aims to search for simple and efficient routes for the synthesis of polynuclear heterocyclic systems having an uracil nucleus in their structure starting with 6-amino-1,3-dimethyluracil (1), which is considered as a versatile starting material of a typical synthon leading to the target polynuclear heterocyclic systems. The newly synthesized triheterocycles appear to be promising antimicrobial agents.It was found that the reaction of compound 1 with some heterocyclic systems having vicinal chlorocyano groups is an interesting one. Thus, when compound 1 was subjected to reaction with 2-chloro-4,6-dimethylpyridine-3-carbonitrile (2) in boiling ethanol containing triethylamine as a base, three possible compounds 3-5 may be produced. The structure of compound 4 was ruled out on the basis of spectral data as IR spectrum of the product exhibited a peak at 2222 cm -1 attributed to the CN function and elemental analysis showed the absence of chlorine. The 1 H NMR spectrum (DMSO-d 6 ) excluded the formation of compound 3 as it displayed a signal at δ 4.70 ppm corresponding to the NH 2 group with the absence of the H-5 signal at δ 5.73 ppm. These confirmed the formation of 2-(6-amino-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-4,6-dimethylpyridine-3-carbonitrile (5). Fusion of compound 5 above its melting point or increasing the reaction time between compounds 1 and 2 led to cycloaddition of the amino group of uracil to the cyano group of the other ring giving rise to 5-amino-2,4,7,9-tetramethylpyrimido[4,5-h][1,6]naphthyridine-8,10(7H,9H)-dione (6) (Scheme 1).

1-Cyanoacetyl-3,5-dimethylpyrazole

“…17 In a similar manner, 1 gives dimethylaminomethylene derivative 15 upon treatment with DMF dimethyl acetal. 18 (…”

Synthesis of some new pyrazolylfuropyrimidinethiones and triazolofuropyrimidinethiones

“…While, the reaction of compound 3 with 4-methylidenedimethyl-amino-2-phenyl-1,3-oxazol-5-one (6) [19], involved ring opening of oxazolone ring and afforded 4-(4-benzoylaminopyrazol-1-yl)-5,6-diphenylfuro[2,3-d]pyrimidine-2(1H)-thione (7). Moreover, polynuclear heterocyclic systems having pyrazolylfuropyrimidinethiones 9 and 11 were synthesized by treatment of compound 3 with 4-methylidenedimethylamino-3-methyl-1-phenylpyrazol-5-one (8) [20], and 3-methylidenedimethylaminoindol-2(1H)-one (10) [21], respectively in absolute ethanol containing catalytic amount of triethylamine (Scheme 1).…”

Ultrasonically Assisted N-Cyanoacylation and Synthesis of Alkyl(4-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2H)-yl)benzoyl)amino Acid Ester Derivatives

“…In the last few years, researchers have been involved in the exploration of the potential of activated nitriles in heterocyclic synthesis. − Especially, cyanoacetic hydrazide has been reported in many literature works as a good intermediate for the synthesis of numerous biologically active heterocyclic compounds and pharmaceutical agents. − …”