Lu, Qinhong,Ku, Mannching Sherry,Chew, Warren,Cheal, Gloria Karen,Hadfield, Anthony F.,Mirmehrabi, Mahmoud
申请号：
ES13150905
公开号：
ES2586435T3
申请日:
2008.10.16
申请国别(地区):
ES
年份:
2016
代理人:
摘要：
A method for preparing (E) -N- {4- [3-chloro-4- (2-pyridinylmethoxy) anilino] -3-cyano-7-ethoxy-6-quinolinyl} -4- (dimethylamino) -2-butenamide anhydrous in the form of a maleate salt comprising the steps of: i) heating (E) -N- {4- [3-chloro-4- (2-pyridinylmethoxy) anilino] -3-cyano-7-ethoxy-6- quinolinyl} -4- (dimethylamino) -2-butenamide and maleic acid at 50-60 ° C in a water solution: n-propanol and keep the mixture at 50-60 ° C for a minimum of 15 min； ii) cooling said solution for at least one hour at 40 ° C and keeping the solution cooled to 40 ° C for 12 hours； iii) further cooling the cooled solution to room temperature, 25 ° C, for a minimum of 4 hours and keeping the solution further cooled to room temperature, 25 ° C, for at least 2 hours； iv) filter the mixture obtained in step iii) to obtain (E) -N- {4- [3-chloro-4- (2- pyridinylmethoxy) anilino] -3-cyano-7-ethoxy-6 maleate salt -quinolinyl} -4- (dimethylamino) -2-butenamide, in which the (E) - N- {4- [3-chloro-4- (2-pyridinylmethoxy) anilino] -3-cyano- maleate salt 7-Ethoxy-6-quinolinyl} -4- (dimethylamino) -2-butenamide crystalline is (E) -N- {4- [3-Chloro-4- (2-pyridinylmethoxy) anilino] -3-cyano- 7-ethoxy-6-quinolinyl} -4- (dimethylamino) -2-butenamide monohydrate； and v) drying the (E) -N- {4- [3-chloro-4- (2-pyridinylmethoxy) anilino] -3-cyano-7-ethoxy-6-quinolinyl} -4- (dimethylamino) -2 maleate - butenamide monohydrate from step iv) under vacuum at a temperature greater than 30 ° C for 12 to 48 hours to obtain (E) -N- {4- [3-chloro-4- (2-pyridinylmethoxy) anilino] -3 maleate -cyano-7-ethoxy-6-quinolinyl} -4- (dimethylamino) -2- crystalline anhydrous butenamide.Un método para preparar (E)-N-{4-[3-cloro-4-(2-piridinilmetoxi)anilino]-3-ciano-7-etoxi-6-quinolinil}-4- (dimetilamino)-2-butenamida anhidra en forma de sal de maleato que comprende las etapas de: i) calentar (E)-N-{4-[3-cloro-4-(2-piridinilmetoxi)anilino]-3-ciano-7-etoxi-6-quinolinil}-4-(dimetilamino)-2-butenamida y ácido maleico a 50-60
