1421823-20-2

Upstream product

• 27143-07-3 ethyl 2-chloro-2-(2-(4-methoxyphenyl)hydrazono)acetate 
• 536760-29-9 3-chloro-1-(4-nitrophenyl)-5,6-dihydropyridin-2(1H)-one 
• 104-94-9 4-methoxy-aniline 
• 503615-03-0 3-(morpholin-4-yl)-1-(4-nitrophenyl)-5,6-dihydropyridin-2(1H)-one 
• 881386-01-2 3,3-dichloro-1-(4-nitrophenyl)piperidine-2-one 
• 38560-30-4 1-(4-nitrophenyl)piperidine-2-one 
• 1039914-85-6 5-chloro-N-(4-nitrophenyl)pentanamide 
• 536759-91-8 4,5,6,7-tetrahydro-1-(4-methoxyphenyl)-6-(4-nitrophenyl)-7-oxo- 1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester 
• 100-01-6 4-nitro-aniline 
• 473927-63-8 ethyl (2Z)-chloro[2-(4-methoxyphenyl)hydrazinylidene]ethanoate 
• 1575-61-7 5-Chlorovaleroyl chloride 

Downstream Products

• 503612-45-1 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carbonitrile 

Relevant academic research and scientific papers

PROCESS FOR PREPARING APIXABAN

The present invention relates to process for preparing apixaban, in particular polymorphic form N-1 thereof, as well as to a method for the preparation of crystalline apixaban, especially apixaban polymorphic form N-1.

Method for preparing apixaban crystal form

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.

A method for preparing [...]

The invention discloses an Apixaban preparation method. The Apixaban preparation method comprises that 1, an intermediate I and an intermediate II undergo a [3+2] cyclization addition reaction under the alkali action to produce a compound B, and the compound B undergoes a morpholine ring removal reaction under the acid condition to produce a compound C, 2, the compound C is reduced by iron powder to form a corresponding amino compound D, 3, the amino compound D and 5-chlorovaleryl chloride undergo an amidation reaction under the triethylamine action to produce a compound E, 4, the compound E undergoes a cyclization reaction under the strong base action to produce a compound F, 5, the compound F undergoes a hydrolysis reaction under the strong base action to produce a corresponding carboxyl compound G, and 6, the carboxyl compound G and CDI undergo a reaction to produce an active intermediate H and the active intermediate H and ammonia water undergo an aminolysis reaction to produce the desired compound A. The Apixaban preparation method has simple processes, does not need strict reaction conditions, has low equipment requirements, has high reaction yield, utilizes stable intermediates thereby solving intermediate storage problems, and effectively improves product purity.

Design, synthesis, and structure–activity relationship of novel and effective apixaban derivatives as FXa inhibitors containing 1,2,4-triazole/pyrrole derivatives as P2 binding element

Four series of novel and potent FXa inhibitors possessing the 1,2,4-triazole moiety and pyrrole moiety as P2 binding element and dihydroimidazole/tetrahydropyrimidine groups as P4 binding element were designed, synthesized, and evaluated for their anticoagulant activity in human and rabbit plasma in vitro. Most compounds showed moderate to excellent activity. Compounds 14a, 16, 18c, 26c, 35a, and 35b were further examined for their inhibition activity against human FXa in vitro and rat venous thrombosis in vivo. The most promising compound 14a, with an IC50(FXa) value of 0.15?μM and 99% inhibition rate, was identified for further evaluation as an FXa inhibitor.