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Updated: Jun 9, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
A practical approach for the preparation of monofunctional azulenyl squaraine dye
Wellington Pham1, Ralph Weissleder, Ching-Hsuan Tung
1Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Abstract:
The synthesis of monofunctional azulenyl squaraine dye NIRQ(700) is described. The essential azulene intermediate 3, 1-(methoxycarbonyl)-2-methylazulene, was achieved via [8+2] cycloaddition between lactone 2, 2H-3-methoxycarbonyl-cyclohepta[b]furan-2-one, and the in situ generated vinyl ethers under high temperature and pressure conditions. Methylation on the cycloheptatriene ring of 2-methyl azulene 6 via Meisenheimer-type intermediate following Schrott's method formed the carboxylic acid intermediate 9, 3-(2-methyl-azulen-4-yl)-propionic acid. Condensation of 9 with squaric acid provided the title compound NIRQ(700) at moderate yields. The non-fluorescent squaraine dye NIRQ(700) absorbed in a 600-700 nm range and potentially can be used to quench a number of available NIR fluorochromes in order to extend the spectrum of biological quenching assays.
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