503614-92-4

Usage

Uses

Used in Pharmaceutical Industry:
1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid is used as an intermediate in the synthesis of Apixaban (A726700) for its role as an inhibitor of blood coagulation factor Xa. This application is significant in the development of anticoagulant medications, which are crucial for the prevention and treatment of various cardiovascular conditions, such as deep vein thrombosis, pulmonary embolism, and stroke.

Upstream product

• 503615-03-0 3-(morpholin-4-yl)-1-(4-nitrophenyl)-5,6-dihydropyridin-2(1H)-one 
• 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 
• 1421823-20-2 ethyl 6-(4-(N-(4-chlorobutyl)carboxamido)phenyl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate 
• 545445-44-1 5,6?dihydro?3?(4?morpholinyl)?1?[4?(2?oxo?1?piperidinyl)phenyl]?2(1H)?pyridone 
• 385425-15-0 1-(2-oxopiperidin-1-yl)-4-iodobenzene 
• 148-24-3 8-quinolinol 
• 503614-56-0 1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3, 4-c]pyridine-3-carboxylic acid ethyl ester 
• 104-94-9 4-methoxy-aniline 
• 881386-01-2 3,3-dichloro-1-(4-nitrophenyl)piperidine-2-one 
• 1039914-85-6 5-chloro-N-(4-nitrophenyl)pentanamide 
• 1575-61-7 5-Chlorovaleroyl chloride 
• 473927-64-9 1-(4-methoxy-phenyl)-6-(4-iodo-phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester 
• 675-20-7 piperidin-2-one 
• 454183-28-9 3-(4-nitrophenylamino)propionic acid ethyl ester 

Downstream Products

• 503612-88-2 1-(4-methoxyphenyl)-3-methyl-6-[4-(2-oxopiperidin-1-yl)-phenyl]-1,4,5,6-tetrahydropyrazolo[3,4-c]pyridin-7-one 
• 1074365-84-6 methyl 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxo-1-piperidinyl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazole-[3,4-c]pyridine-3-carboxylate 

Relevant academic research and scientific papers

Method for Preparation of Apixaban

The present invention relates to a novel method for manufacturing apixaban. According to the method of the present invention, the method does not use expensive reagents or solvents, thereby being economical. In addition, there is no special condition or complicated process, and dangerous reagents or solvents are not used, thus the method is easy for mass-production industrially. Furthermore, since no toxic solvents are used in the final step of the synthesis and purification of apixaban, it is possible to manufacture a high purity apixaban with a high yield without the risk of residual solvent.COPYRIGHT KIPO 2020

Preparation method for apixaban acid impurity

The invention discloses a preparation method for an apixaban acid impurity, belonging to the technical field of pharmaceutical and chemical industry. The preparation method comprises the following steps: under alkaline conditions, hydrolyzing ethyl carboxylate or methyl ester (III) into carboxylate, then adding inorganic acid and carrying out treatment so as to obtain the target product (II). According to the invention, raw materials used in the preparation are easily available; preparation process is simple; and the prepared apixaban acid impurity has high yield of 85.4% and high purity of 98.9%, and can be used for qualitative and quantitative analysis of impurities in the production of apixaban, so the quality of apixaban can be better controlled and drug safety is improved.

Design, synthesis, and biological activity of novel tetrahydropyrazolopyridone derivatives as FXa inhibitors with potent anticoagulant activity

A series of novel tetrahydropyrazolopyridone derivatives containing 1,3,4-triazole, triazolylmethyl, and partially saturated heterocyclic moieties as P2 binding element was designed, synthesized, and evaluated in vitro for anticoagulant activity in human and rabbit plasma. All compounds showed moderate to significant potency, and compounds 15b, 15c, 20b, 20c, and 22b were further examined for their inhibitory activity against human FXa in vitro. While compounds 15c and 22b were tested for rat venous thrombosis in vivo. The most promising compound 15c, with an IC50 (FXa) value of 0.14?μM and 98% inhibition rate, warranted further investigation as an FXa inhibitor.

Apixaban derivatives as well as preparation method and application thereof

The invention belongs to the technical field of medicines and discloses apixaban derivatives and analogues as well as a preparation method and application thereof. The structure of the compounds is shown as the following formula. Cheap and readily available paranitroaniline serves as an initial raw material. The preparation method comprises the following steps: performing amidation-cyclization, chlorination, condensation-elimination, cyclization-elimination, reduction, amidation-cyclization so as to obtain a key intermediate; and dehydrating, performing ammonolysis or chlorination, and condensing to synthesize the target compound. The method is simple in operation, convenient in after-treatment and high in yield. The in-vitro anti-coagulant activity of the target compound is investigated by determining the activated partial thromboplastin time (APTT) and thromboplastin time (PT). The EC2X(APTT) of result compounds APX-02, APX-15 and APX-16 is respectively 2.15mug/L, 3.65mug/L and 2.35mug/L, the EC2X(PT) of the result compounds is respectively 0.12mug/L, 3.57mug/L and 1.57mug/L, which are higher than the EC2X(APTT) value of 3.78mug/L and the EC2X(PT) value of 1.59mug/L of a positive control agent Apixaban. The compounds have high anti-coagulant activities. The EC2X(APTT) value of the rest compounds is between 5mug/L and 65mug/L, and the EC2X(PT) value is between 3mug/L and 18mug/L. The structural formula is as shown in the specification.

LACTAM-CONTAINING COMPOUNDS AND DERIVATIVES THEREOF AS FACTOR XA INHIBITORS

The present application describes lactam-containing compounds and derivatives thereof of Formula I: P4—P-M-M4??I or pharmaceutically acceptable salt forms thereof, wherein ring P, if present is a 5-7 membered carbocycle or heterocycle and ring M is a 5-7 membered carbocycle or heterocycle. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.

Compound purification method (by machine translation)

The invention provides a purification type 1 as shown in the method, the method comprises the alkali and alcohol mixed solution of formula 1 compound contact is shown. The method can efficiently purification type 1 indicated by the compound. (by machine translation)

PROCESS AND INTERMEDIATE FOR THE PREPARATION OF APIXABAN

The invention relates to a preparation process and an intermediate compound for the preparation of 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,5,6,7-tetrahydro-1H- pyrazolo[3,4-c]pyridine-3-carboxamide (apixaban) of formula 1. Further, the invention is the cesium salt of 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1- yl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid of formula 4b - where M is cesium ion - and the ammonium salt of 1-(4-methoxyphenyl)-7-oxo-6-[4-(2- oxopiperidin-1-yl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]piridine-3-carboxylic acid of formula 4b - where M is ammonium ion.

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.

A method for synthesizing [...]

The invention discloses a synthetic method of novel Apixaban. The method comprises the following steps: (i) hydrolyzing an Apixaban precursor compound (II) to obtain a carboxylic acid product; and (ii) mixing the carboxylic acid product obtained in the step (i) with ethyl chloroformate, reacting in the presence of diisopropylethylamine at the temperature of 0-5 DEG C for 3-5 hours; then introducing ammonia gas and reacting to obtain an ammonolysis product, namely, Apixaban. By adopting the method for preparing Apixaban by using the Apixaban precursor compound (II), the yield of Apixaban can be up to 93 percent. In the entire synthesis route, the minimum yield in each step is over 76 percent at least, and the total yield is about 33 percent. In the entire process, the use of precious catalysts or auxiliary reagents is avoided.

PROCESS FOR THE PREPARATION OF APIXABAN

The object of the invention is a process for the preparation of 1-(4-methoxyphenyl)-7-oxo-6-[4- (2-oxopiperidin- 1-yl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid amide of formula 1 (apixaban), as well as the intermediates used in the process.