Pyrimidinones 5-unsubstituted

Alkylation at the 6-position can also be achieved with N -unsubstituted 4-pyrimidinones, via a dianion, when there is an electron-withdrawing group also present at the 6-position. Thus, alkylation of the chiral pyrimidinone 514 (At = -chlorophenyl) gave a 54% yield of the enantiomerically pure methyl derivative 516 via the dianion 515 <1999JOC7885>. 

Factors influencing the choice of synthetic routes to pyrimidines depend very much upon the substitution pattern of the desired product. For pyrimidines unsubstituted at the 4- and 6-positions, a two-component ring synthesis reaction involving a 1,3-dialdehyde and a urea or amidine derivative is the most straightforward route, but only if the dialdehyde is readily available. For example, synthesis of 2-chloro-5-(2-pyridyl)pyrimidine 989, an intermediate in the synthesis of a selective PDE-V inhibitor, was achieved in two steps in 40% overall yield by condensation of 2-(2-pyridyl)malondialdehyde 987 with methylurea, followed by demethylation/chlorination of the pyrimidinone 988 with a mixture of POCI3 and PCls <20070PD237>. 

The electron impact mass spectra of N-unsubstituted 4-pyrimidinones indicate the predominance of the two oxo tautomers compared to the hydroxy form (90OMS115). 

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