A New Study On Friedel-Crafts Alkylation Reaction Of 7-Azaindoles

The scaffold of the azaindole is very important in pharmaceutical field, especially the 3-substituted derivatives of the azaindole play important role in keeping the biological activity.However, the synthetic method for this kind of compound is limited. To further explore the Structure-Activity Relationship for this type of compounds, the development of a more efficient synthetic method is necessary.Friedel-Craft alkylation reaction is a good method to install a substitution on the Aromatic ring. However, most of the Friedel-Craft reactions were fucused on the Indole type of compound. To our knowledge, there was no report for the Friedel-Craft reaction of the unprotected 7-azaindole type of compounds. After screening of the Friedel-Craft reaction conditions which work with Indole type of compound, most of the conditions didn’t work well. After screening more conditions, TfOH was found to give the highest yield. Optimization of the new condition give the best condition for the Friedel-Craft reaction with 7-azaindole type of compounds. Application of the reaction into the total synthesisof the compound 3-(1-(2,6-dichloro-3-fluorophenyl)ethyl)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine, we efficiently got the final product.Overall, a novel efficiently synthetic method was developed in the thesis and the method was successfully applied into the total synthesis of the compound 3-(1-(2,6-dichloro-3-fluorophenyl)ethyl)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrrolo [2,3-b]pyridine.