Nucleophilic substitution of 5-bromotriazoloisoquinoline (3) and of 7-bromo-3-methyltriazolopyridine (6) proceeds readily to give a range of 5-substituted triazoloisoquinolines (4a)-(4e), and of 7-substituted triazolopyridines (7a)-(7h) respectively. Triazoloisoquinolines have been converted into 1,3-disubstituted isoquinolines (II)-(13), (15), and (16), and triazolopyridines into 2,6_disubstituted pyridines (17)-(19). Of secondary amine nucleophiles, only piperidine reacted with 7-bromo-3-methyltriazolopyridine (6) to give the 7-substituted derivative (79). A second product in this reaction was a 2,6-disubstituted pyridine (8); the similar compounds (20)-(24) were the only products when morpholine or N-acetylpiperazine were used. The reaction between 7-bromotriazolopyridine (9) and piperidine or morpholine gave in high yield the 2,6_disubstituted pyridines (25) and (26). We have reported 2-4 that triazolopyridine (1) and triazoloisoquinoline (2) can be regiospecifically lithiated; subsequent reaction with electrophiles give respectively 7-substituted triazolopyridines and 5-substituted triazoloisoquinolines. Since we have also discovered methods to open the five membered rings with loss of nitrogen5 the overall process is the equivalent of a regiospecific synthesis of 2,6_disubstituted pyridines or of 1,3_disubstituted
isoquinolines by electrophilic attack on the P-substituted pyridine or l-substituted isoquinoline.
If the synthesis were to be completely general it would require a method to introduce nucleophiles into the triazolo-pyridine or -isoquinoline. We have now achieved this generality, by using