Pyrazine amination

Treatment of a-hydroxy-ketones or -aldehydes with ammonium acetate (65BSF3476, 68BSF4970) results in the formation of dihydropyrazines, presumably by direct amination of the hydroxyketone followed by self-condensation (79AJC1281). Low yields of pyrazines have been noted in the electrolysis of ketones in admixture with KI and ammonia, and again it appears probable that the a-aminoketone derived by way of the a-iodoketone is the intermediate (69CI(L)237>. 

A side chain 7-[3-(mesyloxymethyl)phenoxy]rnethyl group of a perhy-dropyrido[l,2-u]pyrazine was converted to 7-[3-(aminomethyl)phenoxy]-methyl groups by the treatment with different amines (99MIP9). 

Amine bound to a Wang-polystyrene resin 381 was acylated with 4-oxo-4Ff-pyrido[l,2-u]pyrazine-3-carboxylic acid in the presence of bromotrispyrrolidinophosphonium hexafluorophosphate and /-Pr2NEt in A-methylpyrrolidone (98MIP16). l-(4-Cyclohexyl-4-r / r-butylaminocarbo-nyl-l-piperidyl)-2-(4-fluorophenyl)ethylamine was acylated with perhydro-pyrido[l,2-u]pyrazine-3-carboxylic acid (01MIP19). An amino group of a macrocyclic compound attached to a solid support was acylated with... 

A side chain carboxyl group in perhydropyrido[l,2-a]pyrazines was obtained from an ester group by acidic or alkalic hydrolysis. A side chain carboxyl group was converted into a carboxamide group by the treatment with an amine in the presence of 1-hydroxybenzotriazole (OOJAP(K)OO/ 86659). 

Methyl 3-(triphenylphosphoranylideneamino)pyrazine-2-carboxylate 33 has been synthesised and used to obtain pteridines 34, 35 by reaction with isocyanates followed by adding alcohols or amines (Scheme 5)<96JCS(P1)247>. 

Analogous photoadditions have been observed on irradiation of pyrimidine and purine bases in ethers and amines. Irradiation of 1,3-dimethylur-acil (314) in tetrahydrofuran leads to the formation of 5- and 6-(tetrahydro-furan-2-yl)-5,6-dihydrouracils 315 and 316.261 Similarly, solvent adducts arising by way of initial hydrogen abstraction have been obtained on irradiation of pyrazine derivatives in diethyl ether or tetrahydrofuran.262 The... 

Aldehydes and the corresponding 2-aminopyridine, pyrazine, or pyrimidine are admixed in presence of a catalytic amount of clay (50 mg) to generate iminium intermediate. Isocyanides are subsequently added to the same container and the reactants are further exposed to MW to afford the corresponding imidazo[l,2-a]pyridines, imi-dazo[l,2-a]pyrazines and imidazo[l,2-a]pyrimidines (Scheme 6.48). The process is general for all the three components, e. g. aldehydes (aliphatic, aromatic and vinylic), isocyanides (aliphatic, aromatic and cyclic) and amines (2-aminopyridine, 2-amino-pyrazine and 2-aminopyrimidine). A library of imidazo[l,2-a]pyridines, imidazo[l,2-ajpyrazines and imidazo[l,2-a]pyrimidines can be readily obtained by varying the three components [151]. 

Strecker aldehyde are generated by rearrangement, decarboxylation and hydrolysis. Thus the Strecker degradation is the oxidative de-amination and de-carboxylation of an a-amino acid in the presence of a dicarbonyl compound. An aldehyde with one fewer carbon atoms than the original amino acid is produced. The other class of product is an a-aminoketone. These are important as they are intermediates in the formation of heterocyclic compounds such as pyrazines, oxazoles and thiazoles, which are important in flavours. 

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