Ethyl 4-chloro-2- pyrimidine-5-carboxylate

One example of the synthesis of a thienopyrimidine commencing with a pyrimidine precursor appeared in 2006. Thus, 4-chloro-5-cyano-6-aryl-2-methylthiopyrimidines react with either ethyl (or f-butyl) 2-mercaptoacetate to afford 5-amino-4-aryl-2-methylthiothieno[2,3-,y]pyrimidine-6-carboxylic acids <2006JMC3888>. 

It was claimed that cyclization of ethyl 2-chloro-5-cyclopropyl-6- [(7V-(4,5-dimethoxy-2-nitrophenyl)methoxy)carbonyl]-A-(2-fluoro-3-hydroxy-l-oxo-2-propen-l-yl)amino nicotinate (321) in boiling aqueous dioxane in the presence of K2C03 overnight yielded l- [(4,5-dimethoxy-2-nitrophe-nyl)methoxy]carbonyl -9-cyclopropyl-3-fluoro-2-oxo-2,6-dihydropyrido[l, 2-u]pyrimidine-7-carboxylate (160) (95MIP1, 96MIP4, 96USP5580872). 

Ethyl 4,5-diamino-2-(dimethylamino)thieno[2,3-z/]pyrimidine-6-carboxylate (142) was prepared in 93% yield from 4-amino-6-chloro-2-(di-methylamino)pyrimidine-5-carbonitrile (143) with ethyl 2-mercaptoacetate in refluxing EtOH-THF (5 1) (2000S255). 

Starting from the corresponding 6-amino-3-methyluracils and the appropriate ethyl 3-chloro-2-formylacrylates, 7,8-disubstitutcd ethyl 3-methyl-2,4-dioxo-2,3,4,8-tetrahydropyrido[2,3-r/]-pyrimidine-6-carboxylates 14 are prepared by heating in dimethylformamide.231... 

A study of nucleophilic displacement reactions of ethyl 2,4,7-trichloropyrido[2,3-t7 -pyrimidine-5-carboxylate revealed that the reactivity is in the order position 4 > 7 > 2 except in the case of aqueous sodium hydroxide, which gave ethyl 7-chloro-2,4-dioxo-l,2,3,4-tetrahy-dropyrido[2,3-zf]pyrimidine-5-carboxylate.318 This order, especially position 4 > 2, is also valid with other leaving groups. 

The cyclization of ethyl 3-(4-chloro-2-substituted-pyrimidin-5-yl)-2-diazo-3-oxopropanoates 4 (prepared from the corresponding pyrimidine-5-carbonyl chlorides and ethyl diazoacetate) in the presence of triphenylphosphane yields the corresponding 7-substituted ethyl 4-hydroxy-pyrimido[4,5-c ]pyridazine-3-carboxylates 544 [for a similar reaction of 4 (R = SMe) with hydrazine hydrate cf. ref 50]. 

Aryl-7-(methylsulfanyl)pyrimido[4,5-c/]pyrimidin-4-ols are obtained from ethyl 4-chloro-2-(methylsulfanyl)pyrimidine-5-carboxylate upon treatment with benzamidines.140... 

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