专利号:WO-2007138613-A3 优先权日:2006-05-25 标题 :A process for synthesis of [6,7-bis-(2-methoxyethoxy)-quinazolin-4-yl]-(3-ethynylphenyl)amine hydrochloride 发明人:CHANDREGOWDA VENKATESHAPPA; RAO GUDAPATI VENKATESWARA; KUSH ANIL KUMAR; REDDY GOUKANAPALLI CHANDRASEKARA 权利人:VITTAL MALLYA SCIENT RES FOUND; CHANDREGOWDA VENKATESHAPPA; RAO GUDAPATI VENKATESWARA; KUSH ANIL KUMAR; REDDY GOUKANAPALLI CHANDRASEKA 摘要:The present invention provides a process for synthesizing [6,7-bis(2-methoxyethoxy)quinazolin-4-yl]-(3-ethynylphenyl)amine hydrochloride (Erlitinib Hydrochloride) having the formula (I) comprising reacting 3,4-dihydroxy benzaldehyde with bromo derivative of ethyl methyl ether to obtain 3,4-bis(2-methoxyethoxy)benzaldehyde having formula (III). This is converted to give 3,4- bis (2-methoxyethoxy)-benzonitrile which on furthur nitration we obtain 4,5- bis (2-methoxyethoxy)-2-nitrobenzonitrile which on nitro reduction we get 2-amino-4,5-bis(2-methoxyethoxy)benzonitrile. Formylation of this compound yields N'-[2-cyano-4,5-bis(2methoxyethoxy)phenyl]-N,N-dimethylformamidine. Coupling of this formamidine with 3-ethynyl aniline gives erlotinib free base. On furthur treatment of this free base with methanolic/ethanolic hydrochloric acid gives us erlotinib hydrochloride.
专利号:WO-2007138613-A2 优先权日:2006-05-25 标题:A process for synthesis of [6,7-bis-(2-methoxyethoxy)-quinazolin-4-yl]-(3-ethynylphenyl)amine hydrochloride
专利号:WO-2007138612-A2 优先权日:2006-05-25 标题 :A process for synthesis of [6,7-bis-(2-methoxyethoxy)-quinazolin-4- yl]-(3-ethynylphenyl)amine hydrochloride
参考标题:Convergent Approach For Commercial Synthesis Of Gefitinib And Erlotinib 作者:Venkateshappa Chandregowda,Gudapati Venkateswara Rao,Goukanapalli Chandrasekara Reddy |发布日期:2007.9.1 摘要:An Efficient, Economical And Large-Scale Convergent Synthesis Of Epidermal Growth Factor Receptor- Tyrosine Kinase Inhibitors Gefitinib (1, Iressa) And Erlotinib (2, Tarceva) Approved By U.S. Fda For The Treatment Of Non-Small-Cell Lung Cancer Is Described. The Formation Of 4-Anilinoquinazolines Are Achieved In A Simple One-Pot Reaction Of Suitable Formamidine Intermediates And Substituted Anilines