Nitrogen Bridgehead Compounds. 48.1 Synthesis and Stereochemistry of 4-Oxo-1,6,7,8,9,9a-hexahydro-4H-pyrido[1,2-a ]pyrimidine-3-carboxamides

István Hermecz, Márton Kajtár, Kálmán Simon, Tibor Breining, Péter R. Surján, Gábor Tóth, Zoltán Mészáros

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Abstract

The synthesis, the UV, CD, and 1H, l3C, and 15N NMR characterization, and the X-ray diffraction analysis of a series of methyl-substituted 4-oxo-1,6,7,8,9,9a-hexahydro-4H-pyrido[1,2-a]pyrimidine-3-carboxamides 5 and 6 are described. Catalytic (H2/Pd-C) and NaBH4 reductions of quaternary salts 3 and enamines 4 led to the formation of the 9a-epimeric cis-trans pairs 5 and 6. NaBH4 reduction of the quaternary salts of type 3 proceeded with high diastereoselectivity to give the thermodynamically more stable epimers. The largest influence of the methyl substituent on the diastereomer ratio was observed in the different reductions of the 6-methyl derivatives 3b and 4b. X-ray diffraction analysis of 5a, 5b, 6b, and 9 revealed that while the N(1) atom is nearly planar, the nitrogen atom of the cyclic amide moiety, N(5), is significantly pyramidal. Due to the nonplanarity of the bridgehead nitrogen, the annelation of the two rings can be of either cis or trans type; this is determined by the substituent at N(1). Hexahydropyridopyrimidinone 9 unsubstituted at N(1) has the two rings trans annelated, whereas in the N(1)-methyl derivatives 5a, 5b, and 6b the ring junction is cis. The CD spectra indicate that the chiroptical properties are determined by the inherent chirality of the chromophoric NC=CCON chain in the pyrimidinone ring.

Original languageEnglish
Pages (from-to)2918-2925
Number of pages8
JournalJournal of Organic Chemistry
Volume50
Issue number16
DOIs
Publication statusPublished - Aug 1985

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ASJC Scopus subject areas

  • Organic Chemistry

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