Greener and more sustainable access to 6,7-dimethoxy-2-aryl-4-aminoquinazolines via microwave-assisted chemo-selective synthesis in bio-renewable solvents
4 affiliations
- 1Sigma Aldrich Chemicals Pvt Ltd #12, Bommasandra-Jigani Link Road Bangalore-560100 India
- 2Centre for Nano and Material Sciences, JAIN (deemed-to-be) University Jain Global Campus, Kanakapura Road Bangalore-562112 India
- 3Department of Chemistry, School of Basic and Applied Sciences, SGT University Gurugram-122505 Haryana India
- 4Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University P. O. Box 84428 Riyadh 11671 Saudi Arabia
Abstract
Developing more sustainable, efficient and environmentally benign protocols towards the construction of promising heterocycles remains a cornerstone of green and sustainable medicinal chemistry. Herein, a two-stage, microwave-assisted, rapid and greener synthesis of 6,7-dimethoxy-2-aryl-4-aminosubstituted-quinazoline derivatives is demonstrated. Chemoselective SNAr at C-4 position of 2,4-dichloro-6,7-dimethoxyquinazoline with primary amines in bio-renewable γ-valerolactone (GVL) solvent delivered 4-amino-2-chloroquinazoline intermediates. Subsequently, a palladium-catalyzed Suzuki–Miyaura cross-coupling at C-2 using ethanol–water (9 : 1) as an eco-friendly medium under microwave irradiation at 100 °C for 120 min, furnished 2-aryl-4-aminosubstituted quinazoline derivatives. Relative to a conventional solvent benchmark for step 2, the optimized platform achieves a 4.8-fold reduction in reaction-step simple E-factor reduction from 18.4 to 3.8 kg kg−1, enhancement in reaction-step process mass intensity to 5.2-fold (8.2 g g−1) from 42.6 g g−1, 80% reduction in reaction time (120 from 480–840 minutes) and achieving an Intrinsic atom economy of 82.2%, addressing seven out of the twelve Anastas–Warner green chemistry principles. This workflow underscores a scalable, solvent-efficient, metal-catalyzed route with reduced environmental impact.
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BibTeX
@article{deokar2026greener,
title = {{Greener and more sustainable access to 6,7-dimethoxy-2-aryl-4-aminoquinazolines via microwave-assisted chemo-selective synthesis in bio-renewable solvents}},
author = {Rhushikesh C. Deokar and Thrilokraj R and Nutan Sharma and Dhananjay Satav and Markus Obkircher and Sadaf Jamal Gilani and Saikat Sinha and Ramesh B. Dateer},
journal = {RSC advances},
year = {2026},
month = nov,
doi = {10.1039/d6ra08343a},
url = {https://europepmc.org/article/PMC/PMC13729383},
note = {CC BY},
}
RIS
TY - JOUR
TI - Greener and more sustainable access to 6,7-dimethoxy-2-aryl-4-aminoquinazolines via microwave-assisted chemo-selective synthesis in bio-renewable solvents
AU - Rhushikesh C. Deokar
AU - Thrilokraj R
AU - Nutan Sharma
AU - Dhananjay Satav
AU - Markus Obkircher
AU - Sadaf Jamal Gilani
AU - Saikat Sinha
AU - Ramesh B. Dateer
PY - 2026
DA - 2026/11/03
JO - RSC advances
DO - 10.1039/d6ra08343a
UR - https://europepmc.org/article/PMC/PMC13729383
AB - Developing more sustainable, efficient and environmentally benign protocols towards the construction of promising heterocycles remains a cornerstone of green and sustainable medicinal chemistry. Herein, a two-stage, microwave-assisted, rapid and greener synthesis of 6,7-dimethoxy-2-aryl-4-aminosubstituted-quinazoline derivatives is demonstrated. Chemoselective SNAr at C-4 position of 2,4-dichloro-6,7-dimethoxyquinazoline with primary amines in bio-renewable γ-valerolactone (GVL) solvent delivered 4-amino-2-chloroquinazoline intermediates. Subsequently, a palladium-catalyzed Suzuki–Miyaura cross-coupling at C-2 using ethanol–water (9 : 1) as an eco-friendly medium under microwave irradiation at 100 °C for 120 min, furnished 2-aryl-4-aminosubstituted quinazoline derivatives. Relative to a conventional solvent benchmark for step 2, the optimized platform achieves a 4.8-fold reduction in reaction-step simple E-factor reduction from 18.4 to 3.8 kg kg−1, enhancement in reaction-step process mass intensity to 5.2-fold (8.2 g g−1) from 42.6 g g−1, 80% reduction in reaction time (120 from 480–840 minutes) and achieving an Intrinsic atom economy of 82.2%, addressing seven out of the twelve Anastas–Warner green chemistry principles. This workflow underscores a scalable, solvent-efficient, metal-catalyzed route with reduced environmental impact.
SN - 2046-2069
ER -