Визначення маскованої основності в імідазо[1,5-a]піридинкарбонових кислотах з використанням естерів

• Date: 2026
• Author Affiliations: Svitlana V. Stetsenko — Taras Shevchenko National University of Kyiv; Enamine Ltd; Galyna P. Grabchuk — Taras Shevchenko National University of Kyiv
• Keywords: keywords
• Main Authors: Stetsenko, Svitlana V., Grabchuk, Galyna P.
• Format: Article
• Language: English
• Published: National University of Pharmacy 2026
• Subjects: імідазо[1,5-a]піридин; карбонові кислоти; естери; потенціометричне титрування; pKa; ЯМР спектроскопія; медична хімія
• Online Access: https://ophcj.nuph.edu.ua/article/view/360150
• Journal Title: Journal of Organic and Pharmaceutical Chemistry

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.