Ring-saturated pyrimidine derivatives

Glowka et al. studied two tetrahydro[l,2,4]triazolo[4,3- ]pyrimidine derivatives 66a and 66b by X-ray diffraction <1994JCX375>. In the solid state, both molecules had the same conformation and were found to be packed in similar manner. The triazole rings proved to be planar, and the conjugation of the Jt-electrons with the lone pair of the N-8 atom was assumed to be the reason of the sofa conformation of the saturated six-membered ring. 

Partial saturation of the pyridazino ring of 3-acylamino-4//-pyrimido[l,2-A pyridazin-4-ones and the pyrazino ring of 3-acylamino-4//-pyrazino[l,2-tf]pyrimidin-4-ones in EtOH/AcOH system using Pd/C catalyst, resulted in the respective 6,7,8,9-tetrahydro derivatives in good yields <2000JHC783>. 

Partly saturated pyrazino[l,2-r-]pyrimidines were prepared by formation of the pyrazine ring. 2-Substituted-8-hydroxy-3,4-dihydro-177,277-pyrazino[l,2-r-]pyrimidin-l-ones were prepared by a [6+0] synthesis involving cyclization of 6-hydroxy-pyrimidine-4-(fV-hydroxyethyl)carboxamides <2005W02005/087766>. The 2/7-pyra-zino[l,2-c]pyrimidine-3-carboxamide 164 (Y = NH) was formed from [5+1] atom fragments via the uracil derivative 163 (Y = NH) and DMF-dimethyl acetal. Compounds 163 were prepared from 6-chloromethyluracil and glycine methyl ester 162 (Y = NH) (Scheme 20) <2004W02004/014354>. 

The continuing interest in the chemistry of the 1,3-oxazines and the related thiazines and pyrimidines may arise in part from their versatile synthetic applicability and their pharmacological usefulness. Although six-membered saturated or partially saturated 1,3-heterocycles and their derivatives fused with a benzene ring have been thoroughly studied since the beginning of the twentieth century, much less attention has been paid to their saturated counterparts, the related cycloalkane-fused bicyclic 1,3-heterocycles. 

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