With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.630125-91-6,4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline,as a common compound, the synthetic route is as follows.
630125-91-6, To a solution of 4- ( (4-ethylpiperazin-1-yl) methyl) -3- (trifluoromethyl) aniline (60 mg 0.209 mmol) in THF (10 mL) was added triphosgene (21.69 mg 0.073 mmol) . The resulting mixture was stirred at 70 . After 30 min TLC analysis (PE/EA 3/1) showed the starting material was disappeared. The solvent was removed in vacuo to give a brown oil of 1-ethyl-4- (4-isocyanato-2- (trifluoromethyl) benzyl) piperazine (65 mg 0.197 mmol 94yield) . To a solution of 4- ( (5-ethoxy-6- ( (4-methoxybenzyl) oxy) pyridin-3-yl) oxy) aniline (50 mg 0.136 mmol) and Et3N (44 mg 0.4 mmol) in THF (10 mL) was added a solution of 1-ethyl-4- (4-isocyanato-2- (trifluoromethyl) benzyl) piperazine (64.1 mg 0.205 mmol) in THF (10 mL) . The resulting mixture was stirred at 70 . After LCMS analysis showed the starting material was disappeared. The solvent was removed in vacuo. The residue was washed with H2O. The residue was purified by preparative TLC to yield a white solid of 1- (4- ( (5-ethoxy-6- ( (4-methoxybenzyl) oxy) pyridin-3-yl) oxy) phenyl) -3- (4- ( (4-ethylpiperazin-1-yl) methyl) -3- (trifluoromethyl) phenyl) urea (50 mg 0.070 mmol 51.2yield) 1HNMR(400 MHz CD3OD) delta 7.85 (d J 2.0 Hz 1H) 7.66-7.64 (m 2H) 7.42-7.36 (m 5H) 6.99-6.95 (m 3H) 6.89 (dd J 6.8 2.0 Hz 2H) 5.29 (s 2H) 4.03-3.98 (m 2H) 3.79 (s 3H) 3.69 (s 2H) 3.31-2.65 (m 8H) 1.37 (t J 7.0 Hz 3H) 1.27 (t J 7.2 Hz 3H) ES-LCMS m/z 680.1 (M+H) .
As the paragraph descriping shows that 630125-91-6 is playing an increasingly important role.
Reference：
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; GLAXOSMITHKLINE (CHINA) R & D COMPANY LIMITED; CHEUNG, Mui; DEMARTINO, Michael P.; EIDAM, Hilary Schenck; GUAN, Huiping Amy; QIN, Donghui; WU, Chengde; GONG, Zhen; YANG, Haiying; YU, Haiyu; ZHANG, Zhiliu; (391 pag.)WO2016/37578; (2016); A1;,
Piperazine – Wikipedia
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