Canertinib dihydrochloride, CI-1033, PD-183805(free base)
卡纽替尼二盐酸盐卡奈替尼Chemical Name: N-[4-(3-Chloro-4-fluorophenylamino)-7-[3-(4-morpholinyl)propoxy]quinazolin-6-yl]-2-propenamide dihydrochloride
CAS No. 289499-45-2, 338796-35-3 (deleted CAS), 267243-28-7 (free base)
项目整合开发状态: Phase II
项目研究机构: Pfizer (Originator)
合成路线: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.
📌 参考资料/链接：
参考文献标题:N-[4-(3-Chloro-4-fluoro-phenylamino)-7-(3-morpholin-4-yl-propoxy)-quinazolin-6-yl]-acrylamide,an irreversible inhibitor of tyrosine kinases
文献作者:Bridges,A.J.; Klohs,W.D.; Driscoll,D.(Pfizer Inc.)
参考来源:EP 1131304; US 6344455; WO 0031048
📄 详细内容
合成路线: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
文献作者: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.
参考来源:J Med Chem 2000,43(7),1380
产品链接: CAS No. 289499-45-2›› 产品链接: CAS No.267243-28-7››