Vol 52, No 2 (2016)

The review compiles the strategies and methods of development of aminopyrimidine derivatives as targeted antitumor pharmaceuticals. The advances in organic and heterocyclic chemistry are considered in the targeted synthesis of aminopyrimidine derivatives whose series contains the most demanded and efficient antitrumor pharmaceuticals. The problems of preparation of compounds with multikinase activity profile and the construction of chimeric molecules are discussed.

Addition of selenium dibromide to 1-hexene, 1-octene, and allylic ethers occurs through the formation of intermediate kinetic anti-Markovnikov adducts that further transform into more thermodynamically stable Markovnikov adducts presumably via seleniranium intermediates. The methanolysis of both Markovnikov and anti-Markovnikov adducts leads to the formation of the same products in approximately the same ratio thus showing that the reaction proceeds through seleniranium intermediates.

Ketoximes formed from ketones in the presence of hydroxylamine and silica gel in formic acid undergo in situ the Beckmann rearrangement under mild conditions affording in high yields the corresponding amides. Unsymmetrical aromatic ketones, methyl aryl ketones, and methyl cyclohexyl ketone under these conditions form as a rule amides mixtures.

Reaction of acetoacetic acid N-arylamides with ninhydrin at boiling in ethanol in the presence of iron(III) chloride afforded 1-aryl-3a,8b-dihydroxy-3-(1-hydroxyethylidene)-1,3,3а,8b-tetrahydroindeno[1,2-b]-pyrrole-2,4-diones. The structure of compounds was confirmed by IR, ¹Н NMR, and mass spectra and X-ray diffraction (XRD) analysis.

Preparation method is developed for a new 6,6'-[piperazine-1,4-diylbis(methylene)]bis[3,5-di(tert-butyl)- 1,2-benzoquinone], including the stage of 3,5-di(tert-butyl)pyrocatechol aminoalkylation by Mannich reaction followed by oxidation. The molecular structure of one of its hydrolysis products, 4,6-di(tert-butyl)-2,3-dihydroxybenzaldehyde, is established by X-ray diffraction (XRD) analysis.

Acylation of 1-methyl-3,3-dialkyl-3,4-dihydroisoquinolines with acid chlorides afforded enaminoketones. Enaminophenylketones from the obtained series were reacted with oxalyl chloride to provide 1-benzoyl-5,5-dialkyl-2,3,5,6- tetrahydropyrrolo[2,1-a]isoquinoline- 2,3-diones. The reaction of the latter with binucleophiles leads to the opening of the pyrrole ring and to the heterocyclization: Under the effect of o-phenyldiamine qinoxaline is formed, 1,2-cyclohexanediamine provides the hexahydro-benzimidazole system, о-aminophenol gives benzoxazole, 3-hydroxy-2-amino-pyridine furnishes oxazolo[4,5-b]pyridine. In the reaction with hydrazine hydrate the acylation occurs with hydrazide formation.

By condensation of 2-aryl-substituted pyrimidin-5-ylpropanoic acids with 1,2-ethanediamine and 1,2-benzenediamine in polyphosphoric acid new derivatives of heterocyclic systems were synthesized: imidazo- and benzo[4',5']imidazo[1',2':1,6]pyrido[2,3-d]pyrimidines. Unlike that the reaction of substituted 2-mercaptopyrimidin-5-ylpropanoic acid with 1,2-benzenediamine in polyphosphoric acid in the presence of equimolar amount of ZnCl₂ proceeds by a tandem mechanism with the formation of 4-methyl-5,6-dihydrobenzo[4',5']imidazo[1',2':1,6]pyrido[2,3-d]pyrimidine-2-thiol and the corresponding disulfide.

Reaction of 4-(1,4-benzodioxan-2-yl)thiazol-2-amine with acid chlorides afforded N-substituted amides which further were reduced into the corresponding amines. A new method was developed of preparation of 2-acetyl-1,4-benzodioxane, the initial compound in the synthesis of thiazolylbenzodioxane and numerous derivatives of this series. The adreno- and sympatholytic as well as antihypoxic effect of the obtained biheterocyclic 1,4-benzodioxane derivatives were investigated.

Reaction of 4,5-dichlorophthalonitrile with 3-phenoxyphenol led to the formation of 4,5-bis(3-phenoxyphenoxy)phthalonitrile. It has underlain the synthesis of 2,3,9,10,16,17,23,24-octakis(3-phenoxy-phenoxy) phthalocyanine and its single and double deck sandwich complexes with erbium. As show the electron absorption spectra the complexes are dissociated in dichloromethane at concentrations below 1 × 10^–5 mol L^–1.