38560-30-4

Usage

Uses

1. Used in Pharmaceutical Industry:
1-(4-Nitrophenyl)-2-piperidinone is used as a key intermediate in the synthesis of inhibitors for blood coagulation factor Xa. These inhibitors play a crucial role in the prevention and treatment of various thrombotic disorders, such as deep vein thrombosis, pulmonary embolism, and acute coronary syndrome. 1-(4-Nitrophenyl)-2-piperidinone's structural characteristics allow for the development of potent and selective factor Xa inhibitors, which can help in reducing the risk of bleeding associated with anticoagulant therapy.
2. Used in Research and Development:
1-(4-Nitrophenyl)-2-piperidinone is also utilized in the research and development of new drugs targeting blood coagulation pathways. Its unique structure makes it a valuable tool for designing and optimizing novel therapeutic agents with improved efficacy, safety, and pharmacokinetic properties. Researchers can use 1-(4-Nitrophenyl)-2-piperidinone as a starting point for the synthesis of various analogs and derivatives, which can be further evaluated for their potential as anticoagulant drugs.

Upstream product

• 675-20-7 piperidin-2-one 
• 350-46-9 4-Fluoronitrobenzene 
• 100-01-6 4-nitro-aniline 
• 1575-61-7 5-Chlorovaleroyl chloride 
• 1039914-85-6 5-chloro-N-(4-nitrophenyl)pentanamide 
• 4509-90-4 5-bromovaleroyl chloride 
• 91131-23-6 5-chloro-pentanoic acid phenylamide 
• 62-53-3 aniline 
• 4789-09-7 1-phenylpiperidin-2-one 
• 5134-88-3 sodium p-nitrobenzenesulphonic acid 
• 99-99-0 1-methyl-4-nitrobenzene 

Downstream Products

• 503615-03-0 3-(morpholin-4-yl)-1-(4-nitrophenyl)-5,6-dihydropyridin-2(1H)-one 
• 1267610-26-3 1-(4-aminophenyl)-3-(morpholin-4-yl)-5,6-dihydropyridin-2(1H)-one 
• 1643330-62-4 5-chloropentanoic acid [4-(5-morpholin-4-yl-6-oxo-3,6-dihydro-2H-pyridin-1-yl)phenyl]amide 
• 545445-44-1 5,6?dihydro?3?(4?morpholinyl)?1?[4?(2?oxo?1?piperidinyl)phenyl]?2(1H)?pyridone 
• 503614-91-3 1-(4-methoxy-phenyl)-7-oxo-6-[4-(2-oxo-piperidin-1-yl)-phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester 
• 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 
• 1423803-24-0 6-(4-aminophenyl)-1-(4-methoxyphenyl)-(4-methoxyphenyl)-7-carbonyl-1H-pyrazolo[3,4-c]-4,5,6,7-tetrahydropyridine-3-amide 
• 1437577-94-0 6-(4-(5-bromopentanamido)phenyl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide 
• 1449510-64-8 6-(4-(5-chloropentanamido)phenyl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide 
• 438056-68-9 1-(4-aminophenyl)piperidine-2-one 

Relevant academic research and scientific papers

Preparation method of apixaban intermediate suitable for industrial production

The invention discloses a synthesis method of an apixaban intermediate suitable for industrial production. The method comprises the following steps: carrying out phase-transfer catalytic amidation reaction on paranitroaniline and 5-chlorovaleryl chloride in an organic phase and water phase two-phase system under an inorganic weakly alkaline condition to obtain an APM01 solution, and adding a sodium hydroxide water solution, and cyclizing in a pot to obtain an APM02 solution; directly carrying out alpha-reactive hydrogen dichlorination on an APM02 organic solution and phosphorus pentachloride after simple acid pickling, liquid separation and drying to obtain an APM03 solution; carrying out condensation-elimination reaction on the APM03 solution and excessive morpholine after simple acid pickling and liquid separation, and carrying out simple crystallization and purification treatment to separate out an APM04 solid, and reducing the APM04 into APM05 by sodium sulfide; and carrying out amidation-cyclization two-step one-pot reaction on the APM05 and 5-chlorovaleryl chloride to prepare a key intermediate APM07. According to the method, the synthesis efficiency of the apixaban intermediate is improved, the reaction is mild, and dangerous NaH and other expensive reagents are not used, so that the production cost is saved, the operation is simple, and the method is suitable for industrial popularization.

Preparation 1-(4- method and application) of -2- n-nitrophenyl-piperidine-one-one-one (by machine translation)

The invention belongs to, the technical field) of medicines . and 1 - (4 - in particular relates, 2 - to a synthesis method of a-1 - (4 - nitrophenyl)-piperidine-2-one and a. synthesis method thereof as well, as a synthesis method thereof 1 - (4 -). (by machine translation)

Preparation method of apixaban and intermediates thereof

The invention discloses a preparation method of apixaban and intermediates thereof. The invention provides a preparation method of an apixaban intermediate I. The preparation method of the apixaban intermediate I comprises the step of performing nucleophilic substitution reaction on an apixaban intermediate II and p-fluoronitrobenzene in an organic solvent in the presence of an alkali to obtain the apixaban intermediate I. The preparation method has short steps, simple and safe operation, simple post-treatment steps, environmental friendliness and high total yield, and the obtained product hashigh purity, low production cost and high atomic utilization, and is suitable for industrial production. The formula is shown in the description.

Synthesizing method of intermediate of Apixaban

The invention belongs to the technical field of synthesizing of medicine intermediates, and particularly relates to a synthesizing method of an intermediate of Apixaban. The method includes the step of making 4-R-aniline and 5-chlorovaleryl chloride make contact for reaction in an inert solvent in the presence of amine quarter alkali to obtain the intermediate, namely 1-(4-R-aniline)piperidine-2-ketone, of Apixaban, wherein the reaction formula is shown as the formula I (the formula I is seen in the description). By means of the synthesizing method, the reaction efficiency and conversion rateof the intermediate of Apixaban are improved, there is no need to add tertiary amine organic base or use expensive NaH cyclization reagents, and production cost is saved.

PROCESS FOR THE PREPARATION OF APIXABAN AND INTERMEDIATES THEREOF

The present invention refers to novel process for the preparation of Apixaban. Further, the invention also related to a process for the preparation of intermediate of Apixaban from very basic and cheap row material i.e. Aniline which is widely commercially available. The present invention provides process for preparation of Apixaban using a different sequence of synthetic steps and does not involve use of Ullmann reaction.

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.

Process for the preparation of apixaban

A crystalline Form N-1 of apixaban substantially free from one or more 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; 7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-1-phenyl-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; or methyl 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate, relative to apixaban by area percentage of HPLC and having a mean particle size equal to or greater than 100 μm.

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.

One anticoagulant [...] method and the preparation of key intermediate

The invention provides a preparation method and a key intermediate of an anticoagulant apixaban. The method comprises the following steps: (1) by taking N-(4-nitrophenyl)-3,3-dichloro-2-oxopiperidine (compound 15) as an initial raw material, carrying out a reduction reaction to obtain a compound 16; (2) carrying out an acylation reaction between the compound 16 and 5-valeryl chloride bromine to obtain a compound 17; (3) reacting the compound 17 to obtain a compound 18 in the presence of a cyclic condensation agent; (4) carrying out an elimination reaction between the compound 18 and alkali to obtain a compound 19; (5) reacting the compound 19 with a compound 4 to obtain a compound 6; and (6) finally performing ammonolysis on the compound 6 to obtain apixaban. The method has the advantages that (1) the synthetic route is more reasonable; (2) an expensive or toxic reagent with high irritation is avoided; (3) reaction by-products are fewer and are easily purified; (4) the total yield is high; and (5) the reaction is suitable for industrial production. The reaction route is shown as the following formula.

A method of preparing intermediates [...]

A disclosed preparation method for an apixaban intermediate comprises the following steps: step (1), performing an amidation reaction shown in the specification on a compound 3 and a compound M in an organic solvent under the effect of an organic alkali to obtain a reaction solution containing a compound 3'; and step (2), under the effect of an inorganic base, directly performing an nucleophilic substitution reaction shown in the specification on the reaction solution obtained in the step (1) to prepare a compound 4, and performing a nitration reaction on the compound 4 under the effect of concentrated sulfuric acid and concentrated nitric acid to prepare a compound 5. The preparation method provided by the invention is low in cost, simple in operation and suitable for industrialization.