Canertinib dihydrochloride, CI-1033, PD-183805(free base)-药物合成数据库

【药物名称】Canertinib dihydrochloride, CI-1033, PD-183805(free base)

化学结构式(Chemical Structure):

参考文献No.	43644
标题:	N-[4-(3-Chloro-4-fluoro-phenylamino)-7-(3-morpholin-4-yl-propoxy)-quinazolin-6-yl]-acrylamide, an irreversible inhibitor of tyrosine kinases
作者:	Bridges, A.J.; Klohs, W.D.; Driscoll, D. (Pfizer Inc.)
来源:	EP 1131304; US 6344455; WO 0031048

合成路线图解说明: 4-Chloro-7-fluoro-6-nitroquinazoline (I) was condensed with 3-chloro-4-fluoroaniline (II) to afford the 4-anilino quinazoline (III). Displacement of the activated fluorine of (III) with the potassium alkoxide of morpholinopropanol (IV) gave the morpholinopropyl ether (V). Subsequent reduction of the nitro group of (V), either using iron dust and acetic acid or catalytic hydrogenation over Raney-Ni, furnished aminoquinazoline (VI). This was finally condensed with acrylic acid (VII), via activation as the mixed anhydride with isobutyl chloroformate or using EDC as the coupling reagent, to provide the title acrylamide.

参考文献No.	570097
标题:	Tyrosine kinase inhibitors.17. Irreversible inhibitors of the epidermal growth factor receptor: 4-(Phenylamino)quinazoline- and 4-(phenylamino)pyrido[3,2-d]pyrimidine-6-acrylamides baring additional solubilizing functions
作者:	Smaill, J.B.; Rewcastle, G.W.; Loo, J.A.; Greis, K.D.; Chan, O.H.; Reyner, E.L.; Lipka, E.; Showalter, H.D.; Vincent, P.W.; Elliott, W.L.; Denny, W.A.
来源:	J Med Chem 2000,43(7),1380

合成路线图解说明: 4-Chloro-7-fluoro-6-nitroquinazoline (I) was condensed with 3-chloro-4-fluoroaniline (II) to afford the 4-anilino quinazoline (III). Displacement of the activated fluorine of (III) with the potassium alkoxide of morpholinopropanol (IV) gave the morpholinopropyl ether (V). Subsequent reduction of the nitro group of (V), either using iron dust and acetic acid or catalytic hydrogenation over Raney-Ni, furnished aminoquinazoline (VI). This was finally condensed with acrylic acid (VII), via activation as the mixed anhydride with isobutyl chloroformate or using EDC as the coupling reagent, to provide the title acrylamide.