L,6,7,8,9,9a-Hexahydro-4-oxo-477-pyrido

Pyrido[2,l-6]benzothiazolium bromide, 4-ethoxy-5a,6,7,8,9,9a-hexahydro-l-methyl-9-oxo-X-ray diffraction, 6, 670 Pyridobenzoxazoles synthesis, 6, 190 Pyridocinnolines ring opening, 3, 240 

Methyl-4-oxo-47/-l,6,7,8,9,9a-hexahydro-47/-pyrido[l,2- ]pyrimidine-3-carboxylate has been N-alkylated <1997WO97/007116>. l-(Hetaryl) derivatives were prepared from l,2,3,4-tetrahydro-67/-pyrido[l,2-tf]pyrimidin-6-ones 

N(l)-Alkylation of 1,6,7,8,9,9a-hexahydro-4-oxo-4//-pyrido[l,2-a]py-rimidine-3-carboxamide 368 was carried out with dialkyl sulfate in water in the presence of sodium hydroxide, with triethyl phosphate in the presence of potassium carbonate at 235°C, and with butyl bromide in boiling ethanol in the presence of potassium carbonate for 30 hours (83SZP635101 85JOC2918). 

Conformations of 4-oxo-1,6,7,8,9,9a-hexahydro-4//-pyrido[l, 2-a]pyrimi-dine-3-carboxylates and -3-carboxamides were studied by semiempirical quantum chemical calculations at the AMI level (97H(45)2175). While 1 -methyl-9a-unsubstituted derivatives adopt a cA-fused conformation, 9a-ethoxy-1 -methyl derivatives adopt a trans-fused one to avoid a serious non-bonding interaction between 9a-ethoxy and 1-methyl groups, which would be present in an alternative cA-fused conformation. 

Perhydropyrido[l,2-a]pyrimidin-2-one was A-alkylated with 1,4-dibro-mobutane to yield a l-(4-bromobutyl) derivative (94MIP6). 6-Methyl-4-oxo-4//-1,6,7,8,9,9a-hexahydro-4//-pyrido[l,2-(2]pyrimidine-3-carboxylate 138 was alkylated with alkyl chlorides 139 to give 1-substituted derivatives 140 (97MIP2). 

The magnitudes of the coupling frequency of the 1,3-dicarbonyl moiety of 4-oxo-4H-, 6,7,8,9-tetrahydro-, l,6,7,8,9,9a-hexahydro-, and perhydro-4-oxo-4/f-pyrido[l,2-a]pyrimidine-3-carboxylates are characterized by shifts and by the intensity differences of the coupled vibration bands in their IR spectra (92MI11). 

Attempts to reduce the quaternary salts of 4-oxo-4//-pyrido[l,2-a]-pyrimidines with sodium borohydride or lithium aluminum hydride remained unsuccessful. At the same time the 6,7,8,9-tetrahydro quaternary salts may readily be reduced with sodium borohydride to the 1-alkyl-1,6,7,8,9,9a-hexahydro derivatives. " Sodium borohydride reduction of the 1,6- and 1,7-dimethyl-3-carbamoyl-4-oxo-6,7,8,9-tetrahydro-4//-pyrido[l,2-a]pyrimidinium salts proceeds stereoselectively and yields the thermodynamically controlled product. The l-methyl-3-carbamoyl-4-oxo-l,6,7,8,9,9a-hexahydropyrido[l,2-a]pyrimidines were also prepared by the catalytic (Pd/C) hydrogenation of the 1,6,7,8-tetrahydro deriva-tives, ° but this reaction led to a diastereoisomeric mixture.  

The relative stereostructure of 9-acetyl-7-hydroxy-l,2-dimethyl-7-meth-oxycarbonyl-4-phenyl-6-oxo-l,4,7,8-tetrahydro-6//-pyrido[l,2-a]pyri-midine-3-carboxylate 122 was justified by an X-ray diffraction analysis (97JOC3109). The stereochemistry and solid state structure of racemic trans-6,9-7/-l,6-dimethyl-9a-ethoxy-9-hydroxy-4-oxo-l,6,7,8,9,9a-hexahydro-4f/-pyrido[l,2-a]pyrimidine-3-carboxylate (123), adopting a c/.v-fused conformation, were determined by X-ray investigations (97H(45)2175). 

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