盐酸厄洛替尼的改良合成
Modified synthesis of erlotinib hydrochloride.
作者信息
Barghi Leila, Aghanejad Ayuob, Valizadeh Hadi, Barar Jaleh, Asgari Davoud
机构信息
Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. ; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
出版信息
Adv Pharm Bull. 2012;2(1):119-22. doi: 10.5681/apb.2012.017. Epub 2012 May 5.
PURPOSE
An improved and economical method has been described for the synthesis of erlotinib hydrochloride, as a useful drug in treatment of non-small-cell lung cancer.
METHOD
Erlotinib hydrochloride was synthesized in seven steps starting from 3, 4-dihydroxy benzoic acid. In this study, we were able to modify one of the key steps which involved the reduction of the 6-nitrobenzoic acid derivative to 6-aminobenzoic acid derivative. An inexpensive reagent such as ammonium formate was used as an in situ hydrogen donor in the presence of palladium/charcoal (Pd/C) instead of hydrogen gas at high pressure.
RESULT
This proposed method proceeded with 92% yield at room temperature. Synthesis of erlotinib was completed in 7 steps with overall yield of 44%.
CONCLUSION
From the results obtained it can be concluded that the modified method eliminated the potential danger associated with the use of hydrogen gas in the presence of flammable catalysts. It should be mentioned that the catalyst was recovered after the reaction and could be used again.
目的
已描述了一种改进且经济的方法来合成盐酸厄洛替尼，它是治疗非小细胞肺癌的一种有用药物。
方法
从3,4 - 二羟基苯甲酸开始，经七步合成盐酸厄洛替尼。在本研究中，我们能够改进其中一个关键步骤，该步骤涉及将6 - 硝基苯甲酸衍生物还原为6 - 氨基苯甲酸衍生物。使用一种廉价试剂如甲酸铵在钯/炭（Pd/C）存在下作为原位氢供体，替代了高压氢气。
结果
该方法在室温下产率为92%。厄洛替尼的合成经7步完成，总产率为44%。
结论
从所得结果可以得出结论，改进后的方法消除了在易燃催化剂存在下使用氢气的潜在危险。应该提到的是，反应后催化剂可回收并可再次使用。
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