Introduction of substituents on the carbocyclic ring

Introduction of substituents on the carbocyclic ring relies primarily on electrophilic substitution and on organometallic reactions. The former reactions are not under strong regiochcmical control. The nitrogen atom can stabilize any of the C-nng o-complexes and both pyrrole and benzo ring substituents can influence the substitution pattern, so that the position of substitution tends to be dependent on the specific substitution pattern (Scheme 14.1). 

Pyrimidine ring substitution Substituent effects on the pyrimidine ring were examined while retaining the 7,8-dimethoxy substitution pattern in the carbocyclic ring (Figure 9). A methyl group in the 3-position (L) decreased intravenous activity by more than 100-fold. Similarly, introduction of carbethoxyalkyl substituents in position 3 (LI and Lll) resulted in compounds which are inactive or considerably less active than the N-unsubstituted analog (XXXV). 

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