Nitriles -pyrimidinones

A process research investigation on p38 MAP kinase inhibitors examined the synthesis (on 7 mol scale) of a group of closely related pyrimidinones such as 37, by condensation of a number of arylacetic esters with 4-cyanopyridine and methyl isothiocyanate. Other nitriles were also examined but were much less successful than 4-cyanopyridine 3-cyanopyridine gave a much lower yield and both benzonitrile and 2-cyanopyridine failed completely <06T11714>. 

In another cyclization procedure for the 1,5-benzodiazodne system, the nitriles (296) are converted to the aminodihydrodiazocines (297) (79CPB2589). Attack of nucleophiles on (297) occurs at the N-5—C-6 bond to give the 3,4,5,6-tetrahydrodiazodnes (298) with NaBH4 and the jS-aminoethylquinazolines (301) on hydrolysis. The diazocines (297) behave as typical amidines. Oxidation leads to the amidoximes (300) which on hydrolysis are converted to 2,1-benzisoxazoles (302), and reaction with diketene leads to the fused pyrimidinones (299 and l-methyl-3-one isomer) (79CPB2927). 

Arylidenemalonitriles react with 6-amino- and 6-hydroxyamino-1,3-dimethyl and 3-methyl-pyrimidinedione to give the derivatives (342 R3 = CN) <84CC1549>. This ring was also constructed by the reaction of /J,y-unsaturated nitriles with 2,4-diamino-6(l/f)-pyrimidinone <89EUP314280). 

Hydrogen chloride 6-Chloro-4(3H)-pyrimidinones from 2 nitrile molecules... 

Pyrimidinones from l-alkoxy-3-siloxy-2-aza-l,3-dienes and nitriles via heterodiene synthesis... 

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