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Tetrahydro‐ and octahydropyrido[1,2‐ a ]pyrimidin‐4‐ones
Author(s) -
Yale Harry L.,
Spitzmiller Ervin R.
Publication year - 1976
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570130422
Subject(s) - chemistry , enamine , tautomer , medicinal chemistry , derivative (finance) , alkylation , sodium hydride , imine , stereochemistry , catalysis , organic chemistry , financial economics , economics
The catalytic hydrogenation of 2‐methyl‐, 1 2,8‐dimethyl‐, 2 , 2,9‐dimethyl‐, 3 , 9‐methyl‐2‐propyl‐, 4 , 2,3,9‐trimethyl‐, 5 , 9‐methyl‐2‐phenyl‐, 6 , 9‐hydroxy‐2‐methyl‐, 7 , 9‐acetoxy‐2‐methyl, 8 , 9‐carboxy‐2‐methyl‐, 16 , 9‐carboethoxy‐2‐methyl‐, 17 , 9‐carbomethoxy‐2‐methyl‐, 18 , and several 9‐carboxamido‐2‐methyl‐, 19, 20 , and 21 , derivatives of the pyrido[1,2‐ a ]pyrimidin‐4‐one heterocycle has led to a series of novel 6,7,8,9‐tetrahydro‐ and fully saturated, octahydro analogs. In deuteriochloroform or DMSO‐d 6 solution, the pmr spectra of the tetrahydro derivatives derived from 1‐7 revealed only the 6,7,8,9‐tetrahydro structures. In the pmr spectra of 16‐21 , there was evidence of a facile 1,3‐prototropic shift of the proton from position‐9 to position‐1, resulting in equilibria between tautomeric species, i.e. ,. The ratio of tautomers present at equilibrium, with the esters, favored the enamine conformation, whereas, with both the carboxylic acid and the amides, the imine structure predominated. Supportive evidence for the enamine structure with the esters was derived also from the ir spectra. Alkylation of the anion derived from the tetrahydro 9‐carbomethoxy derivative with sodium hydride led exclusively to derivatives of 6,7,8,9‐tetrahydro system.