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CAPLUS COPYRIGHT 2013 ACS
||Process for preparation of 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-[[1-(N-methylcarbamoylmethyl)piperidin-4-yl]oxy]quinazoline
||Boardman, Kay Alison; Cunningham, Oliver Robert; Goundry, William; Laffan, David Dermot Patrick
||AstraZeneca AB, Swed.; AstraZeneca UK Limited
||PCT Int. Appl., 46 pp. CODEN: PIXXD2
The present invention pertains to a process for the prepn. of 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-[[1-(N-methylcarbamoylmethyl)piperidin-4-yl]oxy]quinazoline and salts thereof. For example, 2-[4-(4-amino-5-cyano-2-methoxyphenoxy)piperidin-1-yl]-N-methylacetamide (prepn. given) was reacted with N,N-dimethylformamide di-Me acetal in 2-methyltetrahydrofuran in the presence of acetic acid at 76 °C for 16 h to afford 2-[4-[5-cyano-4-[[(dimethylamino)methylene]amino]-2-methoxyphenoxy]piperidin-1-yl]-N-methylacetamide. The intermediate obtained above was reacted with 3-chloro-2-fluoroaniline in methoxybenzene in the presence of acetic acid at 90°C for 20 h to give the title compd. as the final product. Pharmaceutical formulations contg. the title compd. as an active ingredient were also disclosed in the present invention.
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