On the reactivity of 4-cyano-1,3-dichloro-7-methyl-5,6,7,8-tetrahydro-2,7-naphthyridine with several amines in different experimental conditions: monosubstitution, disubstitution, and a new unexpected rearrangement

• Published in: Tetrahedron 2014-08, Vol.70 (33), p.4891-4902
• Main Authors: Sirakanyan, Samvel N., Kartsev, Viktor G., Spinelli, Domenico, Geronikaki, Athina, Noravyan, Azat S., Hovakimyan, Anush A., Panosyan, Henrik A., Ayvazyan, Armen G., Tamazyan, Rafael A.
• Format: Article
• Language: English
• Subjects: 1-Oxo-3,4-dihydro-2,7-naphthyridines; 5,6,7,8-Tetrahydro-2,7-naphthyridines; Amines; Chlorine; Derivatives; Mono- and di-amino 2,7-naphthyridines; Nucleophiles; Nucleophilic substitution; Ring-into-ring rearrangement; Solvents; Synthesis; Tetrahedrons; X-rays
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2014.05.070

The reactivity of 4-cyano-1,3-dichloro-7-methyl-5,6,7,8-tetrahydro-2,7-naphthyridine 1 with nucleophiles has been investigated. The different reactivity of the two chlorine atoms in 1 enabled us to obtain, by using different experimental conditions, the mono- and the di-amino-substituted derivatives of 5,6,7,8-tetrahydro-2,7-naphthyridines 2 and 3, respectively. Thus, by carrying out the reaction in a low-boiling solvent and in the presence of a quasi-stoichiometric amount of amine, the mono-substituted derivatives 2 were obtained, which under harsher conditions was transformed into the diamino derivatives 3 when using an excess of amine. During the synthesis of some diamino derivatives 3 a new rearrangement was observed with formation of 1-oxo derivatives of 3,4-dihydro-2,7-naphthyridines 4. The structure of the unexpected compounds 4 was confirmed by X-ray crystallography. A mechanism for the rearrangement is tentatively suggested. [Display omitted] The reactivity of 4-cyano-1,3-dichloro-7-methyl-5,6,7,8-tetrahydro-2,7-naphthyridine 1 with some primary and secondary amines has been investigated. In some instances an unexpected rearrangement was observed with formation of 1-oxo derivatives of 3,4-dihydro-2,7-naphthyridines 4.