Ethyl-3-aminocrotonate

In many pyrimidine ring syntheses, it is possible or even desirable to isolate an intermediate ripe for ring-closure by the formation of just one bond. For example, ethyl 3-aminocrotonate (502) reacts with methyl isocyanate to give the ureido ester (503) which may be isolated and subsequently converted into 3,6-dimethyluracil (504) by the completion of one bond. However, viewed pragmatically, the whole synthesis involves the formation of two bonds and therefore is so classified. On such criteria, only two pyrimidine/quinazoline syntheses involve the formation of only one bond. 

In 1929, Nenitzescu reported that p-benzoquinone (4) was treated with ethyl 3-aminocrotonate (5) in boiling acetone to yield ethyl 5-hydroxy-2-methylindole-3-carboxylate (6). ... 

At least two pathways have been proposed for the Nenitzescu reaction. The mechanism outlined below is generally accepted." Illustrated here is the indolization of the 1,4-benzoquinone (4) with ethyl 3-aminocrotonate (5). The mechanism consists of four stages (I) Michael addition of the carbon terminal of the enamine 5 to quinone 4 (II) Oxidation of the resulting hydroquinone 10 to the quinone 11 either by the starting quinone 4 or the quinonimmonium intermediate 13, which is generated at a later stage (HI) Cyclization of the quinone adduct 11, if in the cw-configuration, to the carbinolamine 12 or quinonimmonium intermediate 13 (IV) Reduction of the intermediates 12 or 13 to the 5-hydroxyindole 6 by the initial hydroquinone adduct 7 (or 8, 9,10). 

The directing influence of the trifluoromethyl group also competes with that of the strongly electron-donating methoxyl group. Thus 2-methoxy-5-trifluoromethyl-l,4-benzoquinone (26) was treated with ethyl 3-aminocrotonate (5) to furnish 25% of each of the two possible isomeric indoles 27 and 28. °... 

The reaction of ethyl 3-aminocrotonate and EMME at 100°C for 40 hr gave diethyl 2-hydroxy-6-methylpyridine-3,5-dicarboxylate in 15% yield (41CB1111). 

Chloro-2-aryl-2//-chromene-3-carbaldehydes, formed from the reaction of flav-4-ones with dimethylformamide (DMF)/POCl3, react with ethyl 3-aminocrotonate under Hantzsch conditions to give ethyl 2-methyl-5-aryl-5H-chromen[3,4-f]pyridine carboxylates in good yields <2001SC2589>. 

Aminoquinoline and ethyl /3-aminocrotonate at 180-190°C for 6 h yielded N,N -di(2-quinolyl)urea. Cyclocondensation of 2-chloroquinoline... 

Tri- or tetra-substituted pyridines were prepared in a one-pot Bohlmann-Rahtz het-eroannulation of ethyl (3-aminocrotonate and an alkynone, which involved a Michael addition-cyclodehydration sequence. The reaction proceeded within just 20 min under single-mode microwave heating conditions (Scheme 3.28)48. 

In 1951 Antaki and Petrow came to the conclusion that the poor yield of the pyrido[l,2-fl]pyrimidines in the reaction of 2-aminopyridines and acylacetates is ascribed to a rearrangement reaction that the intermediate 2-acylacetamidopyridines undergo. This is also the reason why 4-oxo-4H and not 2-oxo-2H isomers are formed.36 In order to provide support for this hypothesis, they worked out an unequivocal synthesis for 37 by reacting 2-bromopyridine and ethyl 3-aminocrotonate and found that the product was identical with that obtained from 2-acetylacetamidopyridine. 

From 2-amino-6-methylpyridine and ethyl 3-aminocrotonate the expected 2,6-dimethyl-4-oxo-4//-pyrido[l,2-a]pyrimidine was not obtained, but instead a urea derivative is formed.36 Ethyl acetoacetate has also been replaced... 

Reaction of 8-valerolactam and ethyl 3-aminocrotonate in boiling phos-phoryl chloride gave 2-methyl-6,7,8,9-tetrahydro-4//-pyrido[l,2-a]pyrim-idin-4-one (91KPS394). 2-terf-Butyl-6,7,8,9-tetrahydro-4/f-pyrido [1,2-a] pyrimidin-4-one 108 was formed when piperidino derivative 107 was allowed to stand in methanol (85JOC166, 85TL3247). 

Dichlorobenzaldehyde Methyl acetoacetate Ethyl-3-aminocrotonate Hydrochloric acid... 

Dichloro-3-nitro-2-pyrazinamine and ethyl 3-aminocrotonate gave 5-(2-amino-1 -ethoxycarbonylprop-1 -enyl)-6-chloro-3-nitro-2-pyrazinamine (107) (Et3N, Pr OH, 20°C, 16 h 62%).788... 

In contrast to earlier results, the adducts formed by condensation of maleimide and ethyl 3-aminocrotonate or 3-aminocrotononitrile are cyclized to pyrrolo(3,4-c)pyridines and not to pyrrolo(2,3-6)pyrroles106 (equation 75). 

Methylhexahydropyrimidoazepin-4-one (420) was obtained both in the reaction of amidine hydrogen sulfate 414 (R = H) with ethyl acetoacetate in ethanoiic sodium ethoxide, and in the reaction of caprolactim methyl ether with ethyl 3-aminocrotonate in boiling ethanol (61ZOB189). 

From 2-amino-6-methylpyridine and ethyl 3-aminocrotonate the expected... 

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