473927-64-9

Basic information

• Product Name: 1-(4-Methoxyphenyl)-6-(4-iodophenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester
• Synonyms: 1-(4-Methoxyphenyl)-6-(4-iodophenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester;Ethyl 6-(4-iodophenyl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate;Apixaban IV;6-(4-iodophenyl)-1-(4-Methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate;Ethyl 6-(4-iodophenyl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-;ethyl 6-(4-iodophenyl)-1-(4-methoxyphenyl)-7-oxo-4,5-dihydropyrazolo[3,4-c]pyridine-3-carboxylate;Ethyl 6-(4-iodophenyl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine;1-(4-Methoxyphenyl)-6-(4-iodophenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl este
• CAS NO: 473927-64-9
• Molecular Formula: C₂₂H₂₀IN₃O₄
• Molecular Weight: 517.31637
• EINECS: 200-258-5
• Mol File: 473927-64-9.mol

Chemical Properties

• Boiling Point: 649.4±55.0 °C(Predicted)
• Appearance: /
• Density: 1.60
• Storage Temp.: 2-8°C(protect from light)
• PKA: -0.78±0.20(Predicted)
• CAS DataBase Reference: 1-(4-Methoxyphenyl)-6-(4-iodophenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: 1-(4-Methoxyphenyl)-6-(4-iodophenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester(473927-64-9)
• EPA Substance Registry System: 1-(4-Methoxyphenyl)-6-(4-iodophenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester(473927-64-9)

Safety Data

• Hazardous Substances Data: 473927-64-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
1-(4-Methoxyphenyl)-6-(4-iodophenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester is used as an intermediate for the synthesis of Apixaban, a potent, direct, selective, and orally active inhibitor of coagulation factor Xa. 1-(4-Methoxyphenyl)-6-(4-iodophenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester plays a crucial role in the development of new oral anticoagulants for the prevention of venous thromboembolism in total hip and knee replacement orthopedic surgeries, as well as in the treatment of patients with venous thromboembolic disorder or atrial fibrillation.
Used in Orthopedic Surgery:
In the field of orthopedic surgery, 1-(4-Methoxyphenyl)-6-(4-iodophenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester contributes to the development of Apixaban, which is a potential new oral coagulant useful for preventing venous thromboembolism in patients undergoing total hip and knee replacement surgeries.
Used in Stroke Treatment:
1-(4-Methoxyphenyl)-6-(4-iodophenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester is also used in the development of Apixaban for stroke treatment, as it helps in the management of patients with venous thromboembolic disorder or atrial fibrillation, reducing the risk of stroke and other thromboembolic events.

Upstream product

• 473927-63-8 ethyl (2Z)-chloro[2-(4-methoxyphenyl)hydrazinylidene]ethanoate 
• 2067-33-6 5-bromopentanoic acid 
• 4509-90-4 5-bromovaleroyl chloride 
• 540-37-4 p-aminoiodobenzene 
• 545445-10-1 3,3-dichloro-1-(4-iodophenyl)-piperidin-2-one 
• 27143-07-3 ethyl 2-chloro-2-(2-(4-methoxyphenyl)hydrazono)acetate 
• 385425-15-0 1-(2-oxopiperidin-1-yl)-4-iodobenzene 
• 473927-69-4 1-(4-iodo-phenyl)-3-morpholin-4-yl-5,6-dihydro-1H-pyridin-2-one 
• 1415831-82-1 1-(4-iodophenyl)piperidine-2,3-dione 
• 1415831-80-9 1-(4-iodophenyl)-3-trimethylsilyloxy-5,6-dihydro-1H-pyridin-2-one 
• 104-94-9 4-methoxy-aniline 

Downstream Products

• 959426-35-8 6-(4-iodophenyl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid 
• 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 
• 543744-69-0 6-(2'-formyl-biphenyl-4-yl)-1-(4-methoxy-phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester 
• 959426-36-9 6-(4-iodophenyl)-1-(4-methoxyphenyl)-N-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide 
• 503614-92-4 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 
• 503612-72-4 ethyl 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxo-1(2H)-pyridinyl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate 
• 503615-34-7 1-(4-methoxyphenyl)-3-methyl-6-[4-(2-oxo-2H-pyridin-1-yl)phenyl]-1,4,5,6-tetrahydropyrazolo[3,4-c]pyridin-7-one 
• 503612-90-6 3-(1-hydroxy-1-methylethyl)-1-(4-methoxyphenyl)-6-[4-(2-oxopiperidin-1-yl)phenyl]-1,4,5,6-tetrahydropyrazolo[3,4-c]pyridin-7-one 
• 503612-89-3 3-hydroxymethyl-1-(4-methoxyphenyl)-6-[4-(2-oxo-2H-pyridin-1-yl)-phenyl]-1,4,5,6-tetrahydropyrazolo[3,4-c]pyridin-7-one 
• 503612-87-1 1-(4-methoxy-phenyl)-3-(1-methyl-1H-imidazol-2-yl)-6-[4-(2-oxo-piperidin-1-yl)-phenyl]-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one 
• 503612-86-0 1-(4-methoxyphenyl)-3-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)-6-(4-(2-oxopiperidin-1-yl)phenyl)-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one 
• 503612-85-9 3-(4,5-dihydro-1H-imidazol-2-yl)-1-(4-methoxyphenyl)-6-[4-(2-oxo-2H-pyridin-1-yl)phenyl]-1,4,5,6-tetrahydropyrazolo[3,4-c]pyridin-7-one 
• 503612-77-9 1-(4-methoxyphenyl)-6-[4-(2-oxo-1(2H)-pyridinyl)phenyl]-3-(1H-tetrazol-5-yl)-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one 
• 503612-76-8 O-Demethylapixaban 

Relevant articles and documents

Pyrazolo[3,4-c]pyridine derivative

The invention relates to a pyrazolo[3,4-c]pyridine derivative. The invention relates to a compound represented by a formula (I), a tautomer thereof, an optical isomer thereof or a pharmaceutically acceptable salt thereof, wherein the formula (I) is shown in the description, and Z, X, RNc, RNd, RNe and RNf are defined according to the claim 1. The invention further relates to the pharmaceutical composition contain the compound. The invention further relates to use of the compound or the pharmaceutical composition in preparing a drug for preventing and/or treating a disease which inhibits positive influence of an Xa factor, particularly use in preparing the drug for preventing and/or treating the disease which inhibits positive influence of the Xa factor under the condition of low hemorrhage risk.

NOVEL PROCESS FOR THE PREPARATION OF A LACTAM-CONTAINING COMPOUND

Provided herein is a novel, commercially viable and industrially advantageous process for the preparation of 1-(4-Methoxyphenyl)-7-oxo-6-[4-(2-oxo-1-piperidinyl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazole-[3,4-c]pyridine-3-carboxamide, in high yield and with high purity, using a novel intermediate 3-chloro-1-(4-iodophenyl)-5,6-dihydropyridin-2(1H)-one.

Novel intermediate and polymorphs of 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,5,6,7-tetra hydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide and process thereof

The present invention provides a novel intermediate as well as novel polymorphs 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 compound represented by the following structural formula-1 and processes for their preparation.

A PROCESS FOR THE PREPARATION OF APIXABAN AND ITS INTERMEDIATES

The present invention discloses the novel process for preparation of Apixaban intermediate formula (D), intermediate formula (E) and preparation of Apixaban from theses intermediates.

A METHOD OF PREPARING APIXABAN

The object of the present solution provides a method preparing apixaban of formula (I) in which ethyl 6-(4-iodophenyl)- 1 -(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo [3,4- c]pyridine-3-carboxylate of formula (III) is reacted with piperidin-2-one of formula (IV) in the presence of a base and a ligand and under catalysis by copper or by copper (II) ions, wherein a phosphoric acid salt is used as the base and an amine from the group of 1,2-diamines is used as the ligand in an aprotic solvent, and ethyl 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxo-1- piperidin-1-yl)phenyl] -4, 5,6,7-tetrahydro-1H-pyrazol-[3,4-c]pyridine-3-carbvoxylate is prepared, which is converted, by reaction with ammonia in a suitable solvent, to apixaban of formula (I), which is isolated and optionally crystallized.

APIXABAN PREPARATION PROCESS

Process for the preparation of apixaban and intermediates useful for the preparation thereof.

PYRAZOLE CARBOXAMIDE INHIBITORS OF FACTOR XA

The present invention relates to new pyrazole carboxamide inhibitors of factor Xa, pharmaceutical compositions thereof, and methods of use thereof.

Discovery 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, BMS-562247), a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation factor Xa

Efforts to identify a suitable follow-on compound to razaxaban (compound 4) focused on modification of the carboxamido linker to eliminate potential in vivo hydrolysis to a primary aniline. Cyclization of the carboxamido linker to the novel bicyclic tetrahydropyrazolopyridinone scaffold retained the potent fXa binding activity. Exceptional potency of the series prompted an investigation of the neutral P1 moieties that resulted in the identification of the p-methoxyphenyl P1, which retained factor Xa binding affinity and good oral bioavailability. Further optimization of the C-3 pyrazole position and replacement of the terminal P4 ring with a neutral heterocycle culminated in the discovery 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, compound 40). Compound 40 exhibits a high degree of fXa potency, selectivity, and efficacy and has an improved pharmacokinetic profile relative to 4.

Synthesis of 4,5-dihydro-pyrazolo [3,4-c] pyrid-2-ones

A novel process and intermediates thereof for making 4,5-dihydro-pyrazolo[3,4-c]pyrid-2-ones of the type shown below from appropriate phenyl hydrazines is described. These compounds are useful as factor Xa inhibitors.

1,4,5,6-TETRAHYDROPYRAZOLO-[3,4,-C]-PYRIDIN-7-ONES USEFUL AS FACTOR XA INHIBITORS

The present application describes 1,4,5,6-tetrahydropyrazolo-[3,4-c]-pyridin-7-ones of the following formula or pharmaceutically acceptable salt forms thereof: wherein ring Rb is 3-amido or 4-methoxy, Ra can be cyano, trifluoromethyl, or amido, and R can be a substituted phenyl, a substituted imidazolyl, or a substituted pyridine. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.