Pyrrolo [2-3-b] Pyridines of Potential Chemotherapeutic Value

Abstract

The methods available for the synthesis of pyrrolopyridines and the biological activity of the pyrrolo [2,3-b] pyridines are reviewed briefly.

The reasons for the synthesis of pyrrolo [2. 3- b] pyridines from a pyrrole precursor are discussed and the possible routes from the available starting materials outlined. The synthesis of pyrrolo [2, 3-b] pyridines was approached by two main routes.

The attempted syntheses of pyrroto|2,3-b] pyridines from 3-substitued 2-aminopyrroles are discussed and a possible explanation of the failure of these reactions is postulated.

The preparation of a series of 2-amino-4-cyanopyrroles and their reaction with 1,3-dicarbonyl reagents to give pyrrolo [2. 3- b] pyridines: is discussed. The two-stage synthesis of pyrrolo[ 2, 3- b] pyridin-4 (7H)- ones from 2-amino-4-cyanopyrroles and diethyl ethoxymethylenemalonate is discussed. The preferred orientation of products obtained from the reaction between 2-amino-4-cyanopyrroles and unsymmetrical dicarbonyl reagents is discussed in terms of a reaction mechanism, The chemistry of the pyrrolo [2,3-3] pyridines is discussed.

¹³C nuclear magnetic resonance spectroscopy 1H-pyrrolo-[2.3-b] pyridine is discussed and the chemical shifts are rationalised in terms of electron density calculations. The ¹³C chemical shifts of 1H-pyrrolo[3,2-b] pyridine and 1H-pyrrolo [3,2-c] pyridine are compared with those of 1H-pyrrolo-[2:3-b] pyriaine. The ¹³C chemical shifts of a series of pyrrolo[2,3-b] pyridine derivatives are recorded, and a comparison of the chemical shift data with available data for methyl-substituted pyridines was made. The comparison of data established the product of the reaction between an aminopyrrole and 4,4-dimethoxybutan-2-one to be a 6-methylpyrrolo |2,3-b| pyridine and not a 4-methylpyrrolo [ 2,3~b] pyridine.
The mass spectra of most of the compounds prepared in this work are recorded and possible fragmentation pathways are postulated.

Date of Award	Oct 1975
Original language	English