Imidazo pyrimidine-8-carboxylates

Reaction of 2 equiv of 2-aminopyridines with 2-hydropolyfluoroalk-2-anoates 351 in MeCN in the presence of NEts at 90 °C for 50 h afforded a mixture of the isomeric 2-oxo-2H- and 4-oxo-4//-pyrido[l,2-n]pyrimidines 110 and 111. Reaction of 3 equiv of 2-amino-pyridines and 2-hydropoly-fluoroalk-2-enoates 351 in MeCN in the presence K2CO3 could be accelerated by ultrasonic irradiation (125W). 2-Amino-6-methylpyridine yielded only 2-substituted 6-methyl-4//-pyrido[l,2-n]pyrimidin-4-ones 111 (R = 6-Me), whereas 2-amino-5-bromopyridine gave a mixture of 7-bromo-4//-pyrido[l,2-n]pyrimidin-4-one (111, R = 7-Br, R = CF2C1) and 2-(chlor-o,difluoromethyl)-6-bromoimidazo[l, 2-n]pyrimidine-3-carboxylate in 44 and 8% yields, respectively (97JCS(P 1)981). Reactions in the presence of K2CO3 in MeCN at 90°C for 60h afforded only imidazo[l,2-n]pyrimidine-3-carboxylates. 

The reaction of 2-aminoimidazole and EMME in boiling acetic acid for 3-6 hr yielded ethyl imidazo[l,2-a]pyrimidine-6-carboxylate (1113, R = R = H) (59JOC779). 

The reaction of 2-amino-l-methylimidazole hydrochloride and EMME by heating in boiling ethanol in the presence of excess triethylamine overnight gave imidazo[l,2-tf]pyrimidine-6-carboxylate (1115, R = H) in 47% yield [82IJC(B)1030]. The similar reaction with 5-nitro-2-amino-1-methyl-imidazole yielded only a condensation product (1114, R = N02), which... 

Data exists for reactions of benzylidenepyruvic acid 26 with 6-chloropyrida-zin-3-amine 309 and with 2-amino-6-(4-methoxyphenyl)-4-oxo-1,2,3,4-tetrahy-dropyrimidine-5-carbonitrile 311 leading to imidazo[l,2-Z ]pyridazine 310 [242] and pyrimido[l,2- ]pyrimidine-2-carboxylic acid 312 [243] (Scheme 3.85). 

Solid-phase syntheses of pyrimidines continue to appear at a rapid pace. A solid-phase synthesis of 4-(2-amino-6-phenylpyrimidin-4-yl)benzamide was directly scaled up in excellent yields and high purity <03OPRD553>. The synthesis of imidazo[l,2-a]pyrimidines 59 via condensation of a solid-supported a-bromoketone and 2-aminopyridines was reported <03TL6265>. Pyrimido[4,5-t/]pyrimidine-2,4(l//,3W) diones have been accessed via a versatile solid-phase synthetic route <03S1739>. A microwave-assisted solid support synthesis of 5-methyl-6-ethylcarboxyIate-2-thioxothieno[3,2-iflpyrimidine-4(l//)-ones from 2-amino-3,5-diethyl carboxylate-4-methylthiophene and monosubstituted thioureas was reported <03BKC1038>. 

Many ring-fused imidazole derivatives have been synthesized by various methods. Domino Michael addition retro-ene reaction of 2-alkoxyiminoimidazolidines and acetylene carboxylates provided a synthesis of 2,3-dihydroimidazo[l,2-a]pyrimidin-5-(l//)-ones <05T5303>. A single step synthesis of 3,5-dialkyl-9-nitroimidazo[l,2-c]quinazolin-2(3//)-ones from simple carbonyl compounds, primary amines or amino acid methyl esters and 2-azido-5-nitrobenzonitrile has been published <05TL5778>. Diels-Alder reaction of azadienes and benzimidazole-4,7-diones afforded imidazo[4,5-g ]quinoline-4,9-dione derivatives <05EJ01903>. Reaction between isocyanides and dialkyl acetylenedicarboxylates in the presence of 4,5-diphenyl-l,3-dihydro-2//-imidazol-2-one provided a one-pot synthesis of 5//-imidazo[2,l-ft][l,3]oxazine derivatives <05T2645>. Microwave irradiation was employed in the synthesis of 1-ary 1-3-acetyl-1,4,5,6-... 

The second method aimed to prepare 6,7-dihydroimidazo[l, 2-u]purin-9-ones 154 from a derivative of 2,3-dihydroimidazo[l,2-u]pyrimidine-5-one, the purine moiety being built up as follows the first step involved reaction of 2-(methylthio)-imidazolinium iodide with a convenient primary amine giving 2-(substituted amino)imidazoline 150 and then with ethyl oximinocyanoacetate and alkali produced 7-amino-2,3-dihydro-6-nitroso-R4,R6,R7-imidazo[l,2-u]pyrimidin-5(8T/)-one 151. Subsequent hydrogenation furnished the diamine 152, acylation and cyclization with boiling carboxylic anhydride originated the final 6,7-dihydro-R2,R4,R6,R7-imidazo[l, 2-u]purin-9(4f/)-one 154. The last two steps can be... 

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