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Updated: Aug 30, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
[3 + 2] cycloaddition reactions of 4-alkyl-3-hydroxy-2H-pyrazolo[4,3-c]isoquinolinium inner salts
Eifion D Phillips1, Simon C Hirst, Matthew W D Perry
1Department of Medicinal Chemistry, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, Leicestershire LE11 5RH, United Kingdom. eifion.phillips@astrazeneca.com
Abstract:
Heating dipolarophiles with 4-alkyl-3-hydroxy-2H-pyrazolo[4,3-c]isoquinolinium hydroxide inner salts results in [3 + 2] cycloaddition across positions 3a and 5 of the aromatic system to give the [3 + 2] cycloadducts in good yield. When the 4-alkyl substituent is a 2-acetate ester and the methylene group can be deprotonated, a second mode of [3 + 2] cycloaddition becomes available for the resulting anion (across the side chain methine group and position 5 of the aromatic system) and occurs under basic conditions, allowing either of two modes of [3 + 2] cycloaddition to be selected by appropriate choice of reaction conditions.
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