Preparation of new pyrido[3,4- b]thienopyrroles and pyrido[4,3- e]thienopyridazines

Abstract

Two new types of pyrido-fused tris-heterocycles ( 1a, b and 2a, b) have been prepared from 3-aminopyridine in five/six steps. A synthetic strategy for the preparation of the novel pyrido[3,4- b]thieno[2,3- and 3,2- d]pyrroles ( 1a, b) and pyrido[4,3- e]thieno[2,3- and 3,2- c]pyridazines ( 2a, b) has been studied. The Suzuki cross coupling of the appropriate 2- and 3-thienoboronic acids ( 3, 4) and 4-bromo-3-pyridylpivaloylamide ( 9) afforded the biaryl coupling products ( 10, 11) in high yields (85%). Diazotization of the hydrolysed (2-thienyl)-coupling product ( 12) and azide substitution gave the 3-azido-4-(2-thienyl)pyridine intermediate (72%, 14). 3-Azido-4-(3-thienyl)pyridine ( 15) was prepared by exchanging the previous order of reactions. The desired β-carboline thiophene analogues ( 1a, b) were obtained via the nitrene by thermal decomposition of the azido precursors ( 14, 15). By optimising conditions for intramolecular diazocoupling, the corresponding pyridazine products (72–83%, 2a, b) were afforded.