Determination of Masked Basicity in Imidazo[1,5-a]pyridine Carboxylic Acids Using Esters

Authors

  • Svitlana V. Stetsenko Taras Shevchenko National University of Kyiv; Enamine Ltd, Ukraine
  • Galyna P. Grabchuk Taras Shevchenko National University of Kyiv, Ukraine https://orcid.org/0000-0001-6632-5762

DOI:

https://doi.org/10.24959/ophcj.26.360150

Keywords:

imidazo[1,5-a]pyridine, carboxylic acids, esters, potentiometric titration, pKa, NMR spectroscopy, medicinal chemistry

Abstract

Imidazo[1,5-a]pyridine carboxylic acids are useful building blocks for medical chemistry, but their synthesis scale-up and isolation depend strongly on pH. For zwitterion-prone representatives, a direct titration of acids does not always reveal the basicity of the heteroaromatic center, which is critical for their further use. Therefore, a series of acids, their corresponding esters, and hydrochlorides were analyzed by the potentiometric titration together with 1H/13C NMR, HPLC, LCMS, and HRMS. The acids showed apparent pKa values of 5.13-6.11, while the esters exposed the basic-center pKa values in the range of 2.75-4.64. NMR data indicate close electronic similarity within the acid/ester pairs, supporting the use of esters as models for acids with masked basicity.

Supporting Agency

  • The work was funded by the National Research Foundation of Ukraine (the grant number 0126U003788; the NRFU registration number 2025.07/0435).

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Published

2026-06-10

How to Cite

(1)
Stetsenko, S. V.; Grabchuk, G. P. Determination of Masked Basicity in Imidazo[1,5-a]pyridine Carboxylic Acids Using Esters. J. Org. Pharm. Chem. 2026, 24, 8-13.

Issue

Vol. 24 No. 2 (2026): Issue in Progress

Section

Original Researches

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