- One-pot conversion of 2-nitrobenzonitriles to quinazolin-4(3H)-ones and synthesis of gefitinib and erlotinib hydrochloride
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A simple and efficient one-pot conversion of 2-nitrobenzonitriles to quinazolin-4(3H)-ones involving reduction, formylation, hydrolysis and cyclization is reported. These quinazolinones have been used for making in economical way the anticancer drug molecules gefitinib (Iressa) and erlotinib HCl (Tarceva).
- Chandregowda, Venkateshappa,Venkateswara Rao, Gudapati,Chandrasekara Reddy, Goukanapalli
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- AN IMPROVED PROCESS FOR THE PREPARATION OF GEFITINIB
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Present invention discloses an improved process for the preparation of gefitinib (4-(3'-chloro-4'-fluorophenylamino)-7-methoxy-6-[3-(4-morpholinyl)propoxy]quinazoline), of formula-I, which comprises: (i) etherification of iso-vanillin with 3-morpholinopropyl halide, (ii) nitration using nitric acid, (iii) oximation, (iv) dehydration, (v) reduction-cum-hydrolysis, (vi) quinazolinone formation, (vii) introduction of a leaving group at C-4 position in quinozolinone, and (viii) condensation with 3-chloro4-fluoroaniline to get the crude gefitinib. Purification of crude gefitinib is achieved via acid/base treatment or by crystallization from solvents such as ethyl acetate, isopropanol, acetonitrile, and methyl ethyl ketone. Formula I, IX, XI, XIII, XV and XVI.
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(2010/02/13)
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