Ethyl 2-amino-4- thiazole-5-carboxylate

Aromatic thioamides react with MeC(0)CHClC(0)C02Et to give a 3 1 ratio of ethyl 5-acetyl-2-aryl-thiazole-4-carboxylates and the isomeric products (2). Modifications of the Hantzsch synthesis continue to appear. Thus, 2-aryl-5-aroyl-thiazoles may be prepared from the JV -thioaroyl-iViV-dimethyl-formamidines ArC(S)N=CHNMea and a-bromo-ketones [strictly speaking, this is a Type F (C—N—C—S + C) synthesis], whilst 5-amino-2-phenyl-l,2,3-thiadiazolium salts [e.g. (3)] and compounds with the general structure RCHgCN (e.g. R = CN or COaEt) yield 4-amino-thiazoles. ... 

Amino-4-mesitylthiazole (179) cannot be nitrated, in contrast with 2-amino-4-f-Bu-thiazole (194). Nitration is also reported to fail with ethyl-2- acetamidothiazol yl -4-carboxylate (58). 

Prior to the 1947 report by Cook and Heilbron on their novel synthesis, 5-aminothiazoles were mostly unknown in the literature. Previous syntheses included the Curtius degradation of ethyl thiazole-5-carboxylates which did not have general applicability there was also difficultly in obtaining the necessary starting materials. During a study on penicillin, Cook and Heilbron found that the reaction between methyl dithiophenylacetate and ethyl aminocyanoacetate gave what was initially believed to be ethyl phenylthionacetamidocyanoacetate 4. However further studies proved the compound to be 5-amino-4-carbethoxy-2-benzyl-thiazole 5, which was basic. 

An intermediate a-bromo-a-formylacetate hemiacetal has been prepared by reaction of ethyl (3-ethoxyacrylate with A-bromosuccinimide (NBS). Cyclizat-ion of the in situ formed hemiacetal with thioureas affords 2-amino-1,3-thiazole-5-carboxylates (Scheme 58).141... 

Preparation 2-amino-4-trifluoromethyl-thiazole-5-carboxylic acid ethyl ester... 

Transformations of ethyl 2-amino-4-(2-ethoxy-2-oxoethyl)thiazole-5-car-boxylate into 5-substituted 2-amino-4-oxo-4,5-dihydrothiazolo[5,4-c]pyr-idine-7-carboxylates 09H2343 in print. 

Further products prepared by the thionyl chloride method in solution are Dolastatin, a thiazole amino acid component (gln)Thz (70% yield) [1110], 4-phenyl-3-furoxanecarbonitrile (55% yield) [1111], ethyl 5-cyano-l-(l,l-dimethyl-ethyl)-lH-pyrazolo-4-carboxylate (61% yield) [1112], ethyl 2-anilino-4-chloro-5-cya-nothiophene-3-carboxylate (77% yield) [1113], and 4-cyanoisoxazole from its oxime tosylate (47% yield) [1114]. 

Thiazolopyrimidine 110, as mitotic kinesin inhibitors for treatment of cancer, was prepared by the cyclization of ethyl 5-amino-1,3-thiazole-4-carboxylate with trimethyl orthobutyrate and benzylamine to afford the [l,3]thiazolo[5,4-... 

Amino-2-(methylthio)thiazole-4-carboxylic acid ethyl ester 195 reacted with benzoyl isothiocyanate (Scheme 86) to furnish thiazolo[5,4-d]pyrimidine-2-one 196 [119],... 

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