503614-91-3Relevant articles and documents
Synthesis method of apixaban intermediate
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Paragraph 0014; 0021-0022; 0023-0024; 0025-0026, (2021/07/14)
The invention discloses a synthesis method of an apixaban intermediate; the high-yield apixaban intermediate II is obtained by changing the reaction conditions of the apixaban intermediate, so that the yield of the apixaban is improved; specifically, raw materials a and b are subjected to an addition reaction in a toluene solution through base catalysis, after the reaction is completed, an elimination reaction is performed under the action of acid, and then a final product II is obtained through the processes of extraction, washing, concentration, refining and the like.
Method for preparing apixaban crystal form
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Paragraph 0058-0059; 0062, (2020/03/17)
The invention relates to a method for preparing an apixaban crystal form N-1. The method is characterized by comprising the following steps: adding an apixaban compound into a 85-95% C1-6alkyl alcohol, performing dissolution, performing crystal separation, performing filtering and washing, and performing drying, so as to obtain the target crystal form N-1. By adopting the technical scheme of the invention, a crystal conversion solvent is simple and easy to obtain, the operation method is simple, the condition is mild, equipment is not specifically required, special reaction condition and equipment are not needed, and the method is applicable to industrial production.
Preparation process of high-purity apixaban
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Page/Page column 4; 8; 10-12, (2020/01/08)
The invention discloses a preparation process of apixaban. The method comprises the following steps of: performing amidation on an initial raw material compound (IV) and delta-valerolactone under pressure; performing a one-pot reaction on the obtained hydroxyl amide and p-toluenesulfonyl chloride (PTSC)to obtain a compound (III); carrying out a reaction with tetrabutylammonium fluoride trihydrateto obtain a cyclization product compound (II); preparing a compound (I) from 2,4-dichlorobenzaldehyde and formamide under the action of sodium methoxide and a molecular sieve; refining the crude product by adopting an optimized ethanol/dichloromethane mixed solvent, so that impurity A is removed well; by means of the method, the apixaban product with high yield and high purity is prepared, whereinthe purity of the apixaban product is not lower than 99.5%, the impurity A does not exceed 0.05%, and any single impurity does not exceed 0.1%.