4-Aminopyrimidine ring condensed

Completion of the total synthesis afforded only six further steps, including the installation of the second 2-aminopyrimidine ring via a second domino sequence. This process presumably involves a conjugate addition of guanidine (2-293) to the enone system of2-292, followed by a cyclizing condensation and subsequent aromatization. Under the basic conditions, the ethyl ester moiety is also cleaved and 2-294 is isolated in form of the free acid, in 89 % yield. Finally, decarboxylation and deprotection of the amino functionality yielded the desired natural product 2-295. 

A compound that includes an aminopyrimidine ring as well as the quaternary salt present in thiamine shows preferential inhibition of absorption of that co-factor by coccidia parasites over uptake by vertebrates. The compound is thus used in poultry where coccidiosis is an economically important disease. Condensation of ethoxymethylenemalononitrile (42-1) with the amidine (42-2) leads to the aminopyrimidine (42-4), probably via the intermediate addition-elimination intermediate (42-3). The nitrile group is then reduced to the methylamino derivative (42-5) by means of hthium aluminum hydride. Exhaustive methylation, for example by reaction with formaldehyde and formic acid, followed by methyl iodide leads to the quaternary methiodide (42-6). The quaternary salt is then displaced by bromine, and the resulting benzyhc-like cylic halide (42-7) is displaced by 2-picoline (42-8). There is thus obtained amprolium (42-9) [43]. 

Condensed 4-aminopyrimidine ring from o-amino- and o-halogeno-nitriles... 

In a series of consecutive steps involving 224 and 225 the new polyhetero-cyclic ring system 226 has been made from 223132 (Scheme 58). N-Heteroaromatic enamino esters, such as 227, and ethoxymethylene cyano-acetate condense to afford the vinylenamino ester 228 with hydrazines a 3-aminopyrimidine is annelated (229)1328 (Scheme 59). 

Pyrido[2,3-(7]pyrimidincs 23, unsubstituted in the 2,4-positions, have been synthesized by condensation of ethyl 4-aminopyrimidine-5-carboxylate with several esters, phenylacetonitrile, phenylacetamide, or malonic ester chloride.173 In the first step, the 4-amino group reacts with the ester, nitrile, or acid chloride function of the cyclization partner, ring closure then being effected by a Dieckmann-type cyclization. 

The most common synthesis of this ring system is the condensation of a 4-aminopyrimidine with an a-halocarbonyl compound or treatment of a 4-halopyrimidine with 2-chloroethylamine, to yield a 4-(2-chloroethyl)amino derivative which can be easily cyclized. Since the mid-1980s, there have... 

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