Synthesis of substituted 3, 4-dihydroquinazolinones via a metal free Leuckart–Wallach type reaction. Issue 1 (23rd December 2020)

• Record Type: Journal Article
• Authors: Bokale-Shivale, Suvarna; Amin, Mohammad A.; Sawant, Rajiv T.; Stevens, Marc Y.; Turanli, Lewend; Hallberg, Adam; Waghmode, Suresh B.; Odell, Luke R.
• Is Part Of: RSC advances. Volume 11:Issue 1(2021)
• Page Start: 349
• Page End: 353
• Publication Date: 2020-12-23
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d0ra10142g
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : A novel cascade cyclization/Leuckart–Wallach type strategy to prepare biologically important 3, 4-dihydroquinazolinones is presented. Abstract : The 3, 4-dihydroquinazolinone (DHQ) moiety is a highly valued scaffold in medicinal chemistry due to the vast number of biologically-active compounds based on this core structure. Current synthetic methods to access these compounds are limited in terms of diversity and flexibility and often require the use of toxic reagents or expensive transition-metal catalysts. Herein, we describe the discovery and development of a novel cascade cyclization/Leuckart–Wallach type strategy to prepare substituted DHQs in a modular and efficient process using readily-available starting materials. Notably, the reaction requires only the addition of formic acid or acetic acid/formic acid and produces H2 O, CO2 and methanol as the sole reaction byproducts. Overall, the reaction provides an attractive entry point into this important class of compounds and could even be extended to isotopic labelling via the site-selective incorporation of a deuterium atom.