Aminocrotonic acid

Condensation of the TV-substituted p-aminocrotonic acid ester 15 with p-benzoquinone (4) has been successfully carried out to furnish the 5-hydroxyindole 29 when the substituent R on the nitrogen of the aminocrotonic acid ester was methyl, ethyl, -propyl, isopropyl, or -butyl, -hexyl, p-cyanoethyl, p-hydroxyethyl, carbethoxymethyl, benzyl, phenyl, o-tolyl, dimethylaminopropyl, y-hydroxypropyl etc ... 

A modihed Hantzsch synthesis has been utilized for the preparation of 1,4-dihydropyridines (Scheme 66). Thus, condensation of formylfurazans 116 with an acetoacetic ester and aminocrotonic acid ester in isopropanol at reflux led to 1,4-dihydropyridine derivatives 117 in about 70% yield (92AE921). Both isomeric furoxan aldehydes reacted in a similar way. 

A process for the preparation of functionalized pyridines from diacetylene and the ethyl ester of /3-aminocrotonic acid and acetylacetonimine (72ZOR1328 75DIS) has been described. Owing to the lower nucleophilicity of nitrogen in the initial enamine esters and enamine ketone, the reaction with diacetylene occurs in the presence of sodium metal (80°C, dioxane, 3 h, yield of up to 20%). 

Acetoacetic acid N-benzyl-N-methyiaminoethyl ester -Aminocrotonic acid methyl ester m-Nitrobenzaldehyde... 

A mixture of 4.98 g of acetoacetic acid N-benzyl-N-methylaminoethyl ester, 2.3 g of aminocrotonic acid methyl ester, and 3 g of m-nitrobenzaldehyde was stirred for 6 hours at 100°C in an oil bath. The reaction mixture was subjected to a silica gel column chromatography (diameter 4 cm and height 25 cm) and then eluted with a 20 1 mixture of chloroform and acetone. The effluent containing the subject product was concentrated and checked by thin layer chromatography. The powdery product thus obtained was dissolved in acetone and after adjusting the solution with an ethanol solution saturated with hydrogen chloride to pH 1 -2, the solution was concentrated to provide 2 g of 2,6-dimethyl-4-(3 -nitrophenyl)-1,4-dihydropyridlne-3,5-dicarboxylic acid 3-methylester-5- -(N-benzyl-N-methylamino)ethyl ester hydrochloride. The product thus obtained was then crystallized from an acetone mixture, melting point 136°Cto 140°C (decomposed). 

Nicardipine Nicardipine, l,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-methyl-2-[(methyl-phenylmethyl)-amino]ethyl ester 3,5-pirididincarboxylic acid (19.3.7), is synthesized in a manner analogous to the synthesis of nifedipine, the only difference being that in the Hantsch synthesis, two different )3-dicarbonyl compounds are used simultaneously with o-nitrobenzaldehyde. During this, one of these in the enamine form of acetoacetic ester is simultaneously used as an amine component. A heterocycUzation reaction is accomplished by reacting, the methyl ester of 8-aminocrotonic acid with the 2-methyl-2-benzyl-aminoethyl ester of acetoacetic acid [24-27]. 

Furo[3,4-r]pyridine derivatives are generated from the reaction of 2,3-dihalopropenyl ketones with the ethyl ester of / -aminocrotonic acid. Initial reaction products are substituted nicotinic acids which can be partially converted into the furopyridines under harsh vacuum distillation conditions (Scheme 12) <2005CHE1009>. 

Peptides that contain 2-aminoacrylic acid and 2-aminocrotonic acid groups absorb in the ultraviolet region, the former at a wavelength maximum of 240 nm, and the latter with a more generalized absorption. At 240 nm, the molar absorptivity is the same (4,200) for the two... 

The 2-aminoacrylic and 2-aminocrotonic acid residues initially produced by alkali are reduced to L-alanine and 2-aminobutyric acid (But) residues, respectively. Use of a further reducing agent is indicated. The results are expressed as decrease or increase in moles of amino acid for the glycopeptides, and as jumoles per g for the glycoproteins. 

In 5 ml of isopropyl alcohol were dissolved 1.5 g (0.01 mole) of 3-nitrobenzaldehyde, 2.6 g (0.01 mole) of l-benzyl-3-acetoacetyloxypyrrolidine, and 1.3 g (0.01 mole) of p-aminocrotonic acid methyl ester and then the solution was refluxed for 8 hours. The solvent was distilled off under reduced pressure, the residue obtained was dissolved in a small amount of chloroform, and the solution was applied to silica gel column chromatography (column diameter 1.5 cm, height 20 cm, and about 200 ml of chloroform was used as the eluent). The eluates were collected and concentrated to give 3.4 g of oily... 

Nitrobenzylideneacetoacetic acid methyl ester p-Aminocrotonic acid isopropyl ester... 

The reaction of a lactim ether with an amino acid ester yields the corresponding amidino acid ester.95 The principal factor determining the rate of this reaction is, probably, the basicity of the amino group. For instance, the condensation of a lactim ether with an ester of aminocrotonic acid appears either to fail21,95 or to proceed in comparatively low yields.70... 

Reis GM, Duarte ID (2007) Involvement of chloride channel coupled GABA(C) receptors in the peripheral antinociceptive effect induced by GABA(C) receptor agonist cis-4-aminocrotonic acid. Life Sci 80 1268-1273... 

As mentioned above, in the case of glutamine or asparagine residues the side-chain amide groups have to be protected or alternatively, preformed and purified active esters have to be used. When unprotected side-chain threonine derivatives are activated, a partial (3-elimination to a-aminocrotonic acid has been reported,f l whereas arginine, either unprotected and protonated or as co-tosyl derivative may cyclize to a 6-lactam during activa-tion.f l... 

Robinson, R. Extension of the theory of addition to conjugated unsaturated systems. II. The C-alkylation of certain derivatives of (i-aminocrotonic acid and the mechanism of the alkylation of ethyl acetoacetate and similar substances. J. Chem. Soc., Abstracts 1916,109, 1038-1046. 

GABAb GABAc Calcium or potassium channels Chloride channel (-)-Baclofen, (22) cis-4-Aminocrotonic acid (CACA 23) cis-2-(Aminomethyl) -cyclo-propane-carboxylic acid (CAMP,24) Protein kinase C BicucuUine- insensitive... 

Pyridines by Enamines. Like 6-aminouracil (243) 3-aminocrotonitrile (245a) and 3-aminocrotonic acid esters (245 b, c), vinylogues of cyanamide or urethane represent stable but acyclic members of enamines with a free amino group. Vinamidinium salts (7) in the presence of sodium methoxide or the related 3,3-diethoxy-... 

Functional groups in the jS-position may lead to priority in notation. For example, 75 is called j5-aminocrotonic acid nitrile and 76 is ethyl j -aminocrotonate. Further examples pertaining to the nomenclature of complex enamines may be found in the next section in Schemes 2 to 5. 

Carbon-11 labelled calcium channel antagonists C-nifedipine, C-nisoldipine, C-nitrendipine and C-CFj-nifedipine possessing vasodilating and hypotensive properties have been synthesized using a modified Hantzsch-type cyclocondensation proce-dure . Condensation of aldehydes 242, 243 and 244 with 3-aminocrotonic acid esters 245, 246, 247 and with acetoacetic ester 248 produced in one pot after 12 hours reflux in dry ethanol the methyl sulphonylethyl protected dihydropyridines 249-252. Deprotection of the carboxylic acids by alkaline hydrolysis followed by conversion into the dihydropyridine monocarboxylic acids 253-256 gave potassium salts in situ, and subsequent methylation with CH3I produced the corresponding labelled title compounds 257-260 (equation 102),... 

Asn and Gin should be coupled with their side-chains protected or in the form of an active ester otherwise the carboxamide group is converted to the corresponding cyano derivative [153]. Likewise, Thr(Bzl) can undergo a /3-elimination yielding a-aminocrotonic acid [199]. 

Aminopentadienones 151, formed by addition of esters and nitriles of 3-aminobut-2-enoic acid (3-aminocrotonic acid) to acetylene-aldehydes or -ketones, cyclize thermally with loss of H2O to the nicotinic acid derivatives 152 ... 

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