| 徐永平,张洋,王宏亮,吴建一.化学通报,2014,77(12):1236-1239. |
| 吉非替尼的合成新工艺研究 |
| Study on The New Synthesis Technology of Gefitinib |
| 投稿时间：2014-03-13 修订日期：2014-04-03 |
| DOI： |
| 中文关键词: 吉非替尼 离子液 醚化 |
| 英文关键词:gefitinib ionic liquid etherification |
| 基金项目:嘉兴市科技局项目(2012AY1074) |
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| 中文摘要: |
| 本文以6-羟基-7-甲氧基喹唑啉-4-酮为起始原料，在离子液催化下与N-(3-氯丙基)吗啉醚化，然后经氯代再与3-氯-4-氟苯胺亲核取代反应得到目标产物吉非替尼，三步反应总收率为68.7%。通过改变反应物配比、离子液用量和反应温度研究了关键中间体3的最佳制备工艺条件：n（1）：n（2）=1.0：1.2；离子液四氟硼-1-甲基-4-丁基咪唑用量为原料1质量的5%；反应最佳温度为95℃；醚化收率约93.6%。该路线具有反应条件温和、分离简单、路线短和总收率较高的特点，为吉非替尼的工业化生产提供了新的科学依据和理论基础。 |
| 英文摘要: |
| A new approach to the synthesis gefitinib was proposed starting from 6-hydroxy-7-methoxyquinazolin-4(3H)-one, followed by etherification with N-(3-chloropropy1)morpholin?in ionic liquid, chlorination and nucleophilic substitution reaction with 3-chloro-4-fluoroaniline, overall yield is 68.7%. The influences of the molar ration of 1 to 2, the quantity of ionic liquid, the reaction time were investigated during the formation of the key intermediate 3. The optimum reaction conditions were n(1):n(2)=1.0:1.2, m([BMIM]BF4)/m(1)=5%, reaction temperature 95℃ and reaction time 5h. Under the optimum conditions, the yield of 3 was 93.6%. The reaction were carried out under mild conditions with higher yields、shorter routes and products were easy to separate, providing new scientific and theoretical basis for the industrial production of gefitinib. |
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