Pyrimidine nitriles, nucleophilic displacement

Pyridine nitriles show normal reactions. However, with rather more electron-deficient rings, such as those in pyrimidine nitriles or pyridinium nitriles, nucleophilic displacement of the CN becomes possible (cf. 561 —> 562, Section 3.2.3.1.2.i). The nucleophilic displacement of CN in cationic ring (692) by dimethylamine is important in the manufacture of 4-dimethylaminopyridine. 

This gives the 4-pyrimidone ring, which is converted into the 4,5-dichloro-6-(l-fluoroethyl)pyrimidine by the action of sulfuryl chloride in the presence of dimethylformamide (DMF) [68]. The chlorine on the 4-position of the pyrimidine ring is substituted with the side chain 2-[4-(trifluoromethyl)phenyl]ethylamine through a nucleophilic substitution reaction [63]. The side chain 2-[4-(trifluoro-methoxy)phenyl]ethylamine is prepared by chloromethylation of trifluorome-thoxybenzene followed by displacement of the chlorine atom with cyanide and reduction of the nitrile with Raney nickel [69]. 

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