Ethoxymethylenemalonic ester

Ethyl 2-ethylthio-4-chloro-5-pyrimidinecarboxylate (XXIIa), as well as the corresponding4-hydroxy-(XXIIb) and 4-amino-(XXIIIa) derivatives, possess-anti-cytogenic activity on Neurospora crassa [223, 224]. Compounds (XXIIIa, b and c) were found to inhibit the conversion of orotic acid to the uridine nucleotides [202]. Ethyl 2-methylthio-4-(halo-substituted anilino)-5-pyrimidinecarboxylates (XXIV), particularly the o-bromo- and the o-chloro- derivatives, substantially inhibit the growth of five experimental mouse tumours (Krebs-2 ascites carcinoma, Ehrlich carcinoma clone 2, leukaemia L-1210, carcinoma 755 and lymphocytic neoplasm P-288) [225]. Compounds of this type are usually prepared by the base catalysed condensation of ethoxymethylenemalonic esters or related derivatives with urea, thiourea, guanidine, or substituted amidine-type analogues [212, 225-237]. 

Ethoxymethylenemalonic ester in ether added with water-cooling over a period of 2 hrs. to a refluxing ethereal soln. of ethyl-MgBr —diethyl (l-ethylpropyl)malonate. Y 80%. (V. du Vigneaud, G. W. Stacy, D.Todd, J. Biol. Chem. 176, 907 (1948).)... 

In 1939, Gould and Jacobs reported the condensation of aniline with acetyl malonic ester (AME) and ethoxymethylenemalonate (EMME), respectively, followed by cyclization of anilinomethylenemalonic ester 13 and 14 in mineral oil to afford the esters 15 and 16. Saponification of the esters gave the known acids 17 and 18, respectively. 

Fluoro-2-methyltetrahydroquinoline (32.2 g,0.2 mol) Is mixed with diethyl ethoxymethylenemalonate, and the mixture is heated at 125°C to 130°C for 3 hours. Polyphosphoric acid (200 g) is added, and the soiution Is gradually heated to 115°C to 120°C in an oil bath with occasional stirring. The temperature is mainteined for 1 hour,then the mixture is poured into 600 ml of water and neutralized with 40% sodium hydroxide solution. The product ester which precipitates is separated by filtration, washed with water and suspended in 2 liters of 10% sodium hydroxide solution. The mixture is heated on the steam bath for 1 hour, treated... 

Amino-6-methvlPVridine Ethoxymethylenemalonic acid diethyl ester Sodium hydroxide Ethyi iodide... 

C,9H2x07) see Tetroxoprim ethoxyiiiethylenemalonic add diethyl ester see under diethyl ethoxymethylenemalonate ethoxymethylenemalononitrile... 

Reaction of diethyl ethoxymethylenemalonate or ethyl cyanoethoxy-methylene acetate with l-phenyl-4-aminopyrazole gave esters 187a, which cyclized in boiling Dowtherm to the corresponding pyridones 188a.158 The... 

Aminopyridazines can also be condensed with /6 -keto esters in the presence of polyphos-phoric acid to give 2ff-pyrimido[l,2-6]pyridazin-2-ones. 3-Ethoxycarbonylpyrimido-[1,2-6 ]pyridazin-4-ones (169) are obtained by the reaction of 3-aminopyridazines (168) with diethyl ethoxymethylenemalonate in the presence of polyphosphoric acid (71JOC2457). 

ETHOXYMETH YNE see EMTOOO ETHOXY METHYL CHLORIDE see CIMOOO ETHOXYMETHYLENEMALONIC ACID, ETHYL ESTER see EEV200... 

Aminopyrazoles react with diethyl ethoxymethylenemalonate to give derivatives such as (140). Strong heating in an inert solvent gives the hydroxy ester (141), from which the... 

Heating equimolar amounts of 5-amino-l-methyIimidazoIe-2(3i/)-thione (391) with diethyl ethoxymethylenemalonate (390) gave the diethyl ester of [(5-amino-2,3-dihydro-l-methyI-2-thioxo-lH-imidazoI-4-yI)methyIene]propanedioic acid (392), which cyclized in 10% aqueous sodium hydroxide to 6-ethoxycarbonyI-3-methyI-2(lH)-thioxoimidazo[4,5-h]pyridin-5(4H)-one (393) (78H(lO)24i). 

Cyclocondensation of 2-amino-4,5,6,7-tetrahydro-3//-azepine (414) (R = H) with ethoxymethylenemalonate, (ethoxymethylene)cyanoacetate, 2-formyl esters, or 3-oxo esters afforded isomeric mixtures of the 4-oxo- (415,... 

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