V. M. Kisel

Synthesis and Biological Properties of Isoquinolines Spirofused with Carbocycles and Heterocycles at Position 4. (Review)

Published data on the synthesis and biological properties of isoquinolines spirofused with carbocycles and heterocycles at position 4 are reviewed. The methods of synthesis are classified according to the formation of the isoquinoline fragment or the carbocycle or heterocycle fused with it during the construction of the spirocyclic system. Data on the biological activity are arranged according to the types of action exhibited by the compounds.

Condensed Isoquinolines. 14. Spirocyclic Systems Containing a Benzo[5,6][1,2,4]thiadiazino[4,3-b]isoquinoline Ring

We propose a convenient preparative method for synthesis of derivatives of novel heterospirane systems with a benzo[5,6][1,2,4]thiadiazino[4,3-b]isoquinoline ring, based on the reaction of 1-(2-bromomethylphenyl)-1-cyclopentanecarbonitrile and 4-(2-bromomethylphenyl)-3,4,5,6-tetrahydro-2H-pyran-4-carbonitrile with o-aminobenzenesulfamide.

Condensed isoquinolines. 12. Synthesis of novel heterocyclic systems containing a partially hydrogenated spiro[isoquinoline-4,4'-(2H)-pyran] fragment

By condensation of 4-(2-bromomethyl)-3,4,5,6-tetrahydro-2H-pyran-4-carbonitrile with anthranilic acid, its derivatives substituted in the benzene ring (esters, nitrile), and with esters of 2-aminothiophene-3-carboxylic acids and 3-amino-5-bromobenzofuran-2-carboxylic acid there have been synthesized novel derivatives which include spiro-linked tetrahydropyran and 5,10-dihydro-3H-pyrimido[1,2-b]isoquinoline fragments. The pyrimidine ring of the latter was annelated by a substituted benzene, thiophene, or 5-bromobenzofuran ring.

Synthesis of spiro[isoquinoline-4,4′-pyran]-3-imines

A method has been developed for the synthesis of 4-[2-(bromomethyl)phenyl] tetrahydro-2H-4-pyrancarbonitrile and a study was carried out on the reaction of this compound with primary amines, which, depending on the conditions, leads to either 4-[2-(R-aminomethyl)phenyl]tetrahydro-2H-4-pyrancarbonitriles or hydrobromides of 2-R-aryl-2,3,2′,3′,5′,6′-hexahydrospiro[isoquinoline-4(1H),4′-pyran]-3-imines.

Condensed isoquinolines. 7.* Synthesis of derivatives of the new heterocyclic system thieno[3′,2′:5,6]-pyrimido[1,2-b]isoquinoline

Abstract4-Oxo-6, 11-dihydro-4H-thieno[3′, 2′.-5,6]-pyrinudo[1, 2-b]isoquinolines have been synthesized by the reaction of o-bromo-methylphenylacetonitrile with esters of substituted 2-aminothiophene-3-carboxylic acids. They were characterized as the hydrobromides and as the fee bases. The tautonterism of the bases in DMSO solution is discussed.

Condensed isoquinolines. Part 6. Synthesis of 5-aryl-7,12-dihydroisoquino[2,3-a]quinazolinium salts

Abstract2-(o-Aroyl)phenyl-1, 4-dihydroisoquinolin-3(2H)-imine hydrobromides have been synthesized by the reaction of o-bromomethylphenylacetonitrile with o-aminobenzophenones. The products were cyclized into 5-aryl-7,12-dihydroisoquino[2,3-a]quinazolinium perhclorates.

Condensed isoquinolines. 9. Alkylation of 7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-ones

The alkylation of 7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-one proceeds at N(6) or C(−) depending on the type of alkylating agent and reaction conditions. C(−)-Alkylation occurs in the presence of base. The secondary alkylation of the 7-alkyl derivatives occurs at the same position under these conditions. Depending on the conditions, the reaction with o-xylylene dibromide leads to spiro[5H-isoquino[2,3-a]quinazolin-7(12H).2′-indane]-5-one or 11-oxo-4b,5,10,16-tetrahydro-11H-10a-azonia-15b-azadibenz[a,e]pleiadene bromide, which are derivatives of new heterocyclic systems.

Condensed isoquinoline. 5. Reaction of the 6-methyl-5-oxoisoquino[2,3-a] Quinazolinium cation with certain nucleophiles

It has been shown that nucleophilic reagents react with the 6-methyl-5-oxoisoquino[2,3-a]quinazolinium cation at the C(2) atom. The structure of the reaction product is determined by the type of reagent. On reaction with sodium borohydride and secondary amines, 12H- and 12-dialkylamino-12H-6-methyl-5-oxo-5, 6-dihydroisoquino[2,3-a]quinazolines are formed. In the case of primary amines the reaction is accompanied by fission of the C(12)-N(t3) bond with the formation of 2-[o-(N-alkylformimidoyl)-benzyl]-3-methyl-4-oxoquinazolines.