Improvement of the Synthesis Technology of Sorafenib Tosylate
10.6039/j.issn.1001-0408.2015.34.14
- VernacularTitle:对甲苯磺酸索拉非尼的合成工艺改进
- Author:
Quan ZHAO
;
Lan LUO
;
Yi YANG
;
Yongjun GAN
;
Yiwu WANG
- Publication Type:Journal Article
- Keywords:
Sorafenib isocyanates;
Synthesis;
Improvement;
1H-NMR
- From:
China Pharmacy
2015;(34):4795-4797
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To improve the synthesis technology of sorafenib tosylate (Ⅰ). METHODS:The intermediate N-methyl-(4-chlorpyridin-2-yl)carboxamide(Ⅳ)was obtained by chlorination and amidation with 2-picolinic acid as the starting com-pound. Meanwhile,N-[4-chloro-3-(triflouromethyl)phenyl]-N′-(4-hydroxyphenyl)urea (Ⅶ) was prepared from aminophenol and 4-chloro-3-trifluoromethyl phenyl isocyanate,which was obtained from 4-chloro-3-(trifluoromethyl)aniline(Ⅴ)by reaction with initiator triethylamine. Sorafenib tosylate was synthesized from Ⅳ and Ⅶ with potassium tert-butoxide by condensation and salt for-mation. The target compound was characterized by 1H-NMR. RESULTS:The target compound was confirmed as Ⅰ,with the over-all yield of 74% [based on 4-chloro-3-(trifluoromethylanilin)]. The purification of chromatogram was 94%. Optimized technology improves yield and simplifies multi-step intermediate decompression,distillation and purification process;the application of initia-tor shortens the duration of reaction. CONCLUSIONS:Ⅰ is prepared successfully,and raw material can be obtained easily and is easy to operate with high yield.