A facile synthesis of substituted 5,11-dihydro[1]benzoxepino[3,4-b]pyridines

Article abstract of DOI:10.1055/s-1997-1503

5-Amino-5,11-dihydro[1]benzoxepino[3,4-b]pyridines (1) show anti-ulcer and antiarrhythmic activity. An efficient method for the preparation of a key intermediate, furo[3,4-b]pyridin-5(7H)-one (4), and the facile synthesis of 1 were described. The reduction of quinolinic anhydride (5) with sodium borohydride in the presence of acetic acid regioselectively gave the lactone 4. Lactone 4 was then reacted with substituted phenols under basic conditions and the resultant products, 2-(phenoxymethyl)-3-pyridinecarboxylic acids (3), underwent Friedel-Crafts cyclizations to produce the 5,11-dihydro[1]benzoxepino[3,4-b]pyridin-5-ones (2). Compounds 2 were then converted to imines with amines and successively reduced with zinc in acetic acid to the desired compounds 1.