摘要
目的研究抗肿瘤药物舒尼替尼的新合成路线。方法以4-氟-2-碘苯胺(3)为原料,经氯乙酰化、膦酰化、Horner-Emmons-Wittig反应得N-[2-(二乙胺基)乙基]-5-[(E)-2-(4-氟-2-碘代-苯胺基甲酰基)-乙烯基]-2,4-二甲基-1H-吡咯-3-甲酰胺(6);6在醋酸钯和三乙胺的作用下,通过分子内5-exo型环合反应得舒尼替尼。结果与结论新中间体及舒尼替尼结构经核磁共振谱和质谱确证,合成路线未见报道。
Aim To explore a novel protocol for the synthesis of antitumor agent sunitinib.Methods Starting from 2-iodo-4-fluoroaniline(3),5-[2-(4-fluoro-2-iodo-phenylcarbamoyl)-vinyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid(2-diethylamino-ethyl)-amide(6) was obtained via chloroacylation,phosphonation and Horner-Emmons-Wittig reaction.Sunitinib(1) was obtained by intramolecular 5-exo-type annulation reaction in the presence of Pd(OAc)2 and Et3N.Results and conclusion The novel intermediates and target compound were identified by NMR and MS spectra,and the process has not been disclosed before.
出处
《中国药物化学杂志》
CAS
CSCD
2010年第2期99-101,共3页
Chinese Journal of Medicinal Chemistry