138401-24-8

Basic information

• Product Name: 4'-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-(1,1'-biphenyl)-2-carbonitrile
• Synonyms: [1,1'-BIPHENYL]-2-CARBONITRILE, 4'-[(2-BUTYL-4-OXO-1,3-DIAZASPIRO[4.4]NON-1-EN-3-YL)METHYL]-;[1,1'-BIPHENYL]-2-CARBONITRILE-4-[(2-BUTYL-4-OXO-1,3-DIAZASPIRO[4.4]NON-1-EN-3-YL)METHYL];4'-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-(1,1'-biphenyl)-2-carbonitrile;4'-[(2-BUTYL-4-OXO-1,3-DIAZASPIRO[4.4]NON-1-EN-3-YL)METHYL]BIPHENYL-2-CARBONITRILE;4'-[(2-N-BUTYL-4-OXO-1,3-DIAZASPIRO[4.4]NON-1-EN-3-YL)METHYL]-[1,1'-BIPHENYL]-2-CARBONITRILE;[1.1'-Biphenyl]-2-carbonitrile-4-[(2-butyl-4-oxo-1.3-diazaspiro[4.4]non-1-en-3-y;4'-[(2-Butyl-4-oxo-1,3-diazasp;4-(2-butyl-1,3-diazaspiro-[4-4] no-1-en-3-yl-methyl)biphenyl-2-carbonitrile
• CAS NO: 138401-24-8
• Molecular Formula: C₂₅H₂₇N₃O
• Molecular Weight: 385.5
• EINECS: 423-500-4
• Product Categories: Chemical intermediate for Sartan;INTERMEDIATESOF;Irbesartan;(intermediate of irbesartan);Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 138401-24-8.mol

Chemical Properties

• Melting Point: 95-97°C
• Boiling Point: 576.5 °C at 760 mmHg
• Flash Point: 302.5 °C
• Appearance: White or off-white crystalline powder
• Density: 1.15
• Vapor Pressure: 0Pa at 20℃
• Storage Temp.: Refrigerator
• Solubility: soluble in Methanol
• PKA: 2.45±0.20(Predicted)
• CAS DataBase Reference: 4'-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-(1,1'-biphenyl)-2-carbonitrile(CAS DataBase Reference)
• NIST Chemistry Reference: 4'-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-(1,1'-biphenyl)-2-carbonitrile(138401-24-8)
• EPA Substance Registry System: 4'-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-(1,1'-biphenyl)-2-carbonitrile(138401-24-8)

Safety Data

• Hazard Codes: N
• Statements: 50/53
• Safety Statements: 60-61
• RIDADR: 3077
• Hazardous Substances Data: 138401-24-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
4'-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-(1,1'-biphenyl)-2-carbonitrile is used as a precursor in the synthesis of acetylcholinesterase inhibitors for the treatment of various neurological disorders. Its application in this field is due to its ability to contribute to the development of drugs that can help improve cognitive functions and memory by inhibiting the enzyme acetylcholinesterase, which is responsible for breaking down the neurotransmitter acetylcholine.
Used in Quality Control of Medications:
In the pharmaceutical industry, 4'-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-(1,1'-biphenyl)-2-carbonitrile is also used for quality control purposes. As an impurity found in Irbesartan (I751000), a medication used to treat high blood pressure and type 2 diabetes, it is essential to monitor and control the presence of this compound to ensure the safety and efficacy of the drug. The application reason for its use in this context is to maintain the quality and purity of the final product, which is crucial for patient safety and the overall effectiveness of the medication.

Upstream product

• 114772-54-2 4'-(bromomethyl)-1,1'-biphenyl-2-carbonitrile 
• 138402-05-8 2-butyl-1,3-diaza-spiro[4.4]non-1-en-4one 
• 544-92-3 copper(I) cyanide 
• 197440-06-5 2-Butyl-3-(2'-iodo-biphenyl-4-ylmethyl)-1,3-diaza-spiro[4.4]non-1-en-4-one 
• 60421-23-0 cycloleucine methyl ester hydrochloride 
• 109-52-4 valeric acid 
• 133690-92-3 [(2'-cyanobiphenyl-4-yl)methyl]amine 
• 141745-71-3 1-pentanoylamino-cyclopentanecarboxylic acid (2'-cyano-biphenyl-4-ylmethyl)-amide 
• 15026-80-9 N-pentanoylaminocyclopentane-1-carboxylic acid 
• 638-29-9 n-valeryl chloride 
• 52-52-8 1-amino-1-cyclopentanecarboxylic acid 
• 70680-21-6 4-methyl-2'-nitrobiphenyl 
• 609-73-4 o-nitroiodobenzene 
• 154542-77-5 4'-bromomethyl-2-iodobiphenyl 

Downstream Products

• 138402-11-6 2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one 
• 138402-10-5 trityl irbesartan 
• 329055-23-4 2-n-butyl-4-spirocyclopentane-1-[((2'-tetrazol-5-yl)biphenyl-4-yl)methyl]-2-imidazolin-5-one hydrochloride 
• 138402-11-6 irbesartan 

Relevant articles and documents

Novel and expeditious microwave-assisted three-component reactions for the synthesis of spiroimidazolin-4-ones

Highly efficient methods for the syntheses of spiroimidazolinones via microwave-assisted three-component one-pot sequential reactions or one-pot domino reactions are described. The efficiency and utility of the methods have been demonstrated by quickly accessing the antihypertensive drug irbesartan (2).

One-pot method for preparing irbesartan

The invention discloses a one-pot method for preparing irbesartan. The method comprises the following steps: with 2-butyl-1,3-diazaspiro[4,4]non-1-ene-4-one hydrochloride and 2-cyano-4'-bromomethylbiphenyl as raw materials, performing a reaction in an aprotic solvent containing an alkaline solution, performing an alkylation reaction under the action of a phase transfer catalyst to obtain 2-butyl-3-[(2'-cyano-1,1'-biphenyl-4-yl)methyl]-1,3-diazaspiro[4,4]non-1-ene-4-one, and performing a cyclization reaction on the 2-butyl-3-[(2'-cyano-1,1'-biphenyl-4-yl)methyl]-1,3-diazaspiro[4,4]non-1-ene-4-one and sodium azide under the action of a cyclization catalyst to obtain the irbesartan. The method has the advantages of simple operation, a short reaction time, high yield, high purity and suitability for industrial production.

Preparation method of irbesartan isomer and irbesartan intermediate

The invention relates to a preparation method of an irbesartan isomer and an irbesartan condensation compound isomer as an irbesartan intermediate. The method comprises the following steps: 1) a phase transfer catalyst and an organic solvent are added to an irbesartan ring compound hydrochloride and biphenyl bromide, a sodium hydroxide solution is added, a reaction liquid is filtered after sufficient reaction of the raw materials, a filter cake is subjected to column chromatographic separation, and the irbesartan condensation compound isomer is obtained; 2) triethylamine hydrochloride, sodium azide and an organic solvent A are added to the irbesartan condensation compound isomer, the materials are heated to 100-130 DEG C and reacted, the sodium hydroxide solution and an organic solvent B are added, the mixture is stirred, left to stand and subjected to organic layer removal, hydrochloric acid is added to an aqueous-layer solution to regulate pH to 3.5-6.0, the solution is stirred and filtered, a filter cake is subjected to recrystallization with an organic solvent C or subjected to column chromatographic separation, and the irbesartan isomer is obtained. The irbesartan isomer impurity and the irbesartan intermediate prepared with the method have higher purity and lower energy consumption and cost. Meanwhile, the preparation method is simple to operate and environment-friendly and has important value in irbesartan production and research.

Synthesis of amido-N-imidazolium salts and their applications as ligands in suzuki-miyaura reactions: Coupling of hetero- aromatic halides and the synthesis of milrinone and irbesartan

A new catalytic system based on palladium-amido-N-heterocyclic carbenes for Suzuki-Miyaura coupling reactions of heteroaryl bromides is described. A variety of sterically bulky, amido-N-imidazolium salts were synthesized in high yields from the corresponding anilines. This catalytic system effectively promoted Suzuki-Miyaura couplings of heteroaryl bromides and chlorides with a range of boronic acids to give the corresponding aryl compounds in high yield. The yield was increased with increasing steric bulkiness of the substituted group. Especially, 1-(2,6-diisopropylphenyl)-3-N-(2,4,6-tri-tert- butylphenylacetamido)imidazolium bromide (4bc) exhibited 850,000 TON in the coupling reaction of 2-bromopyridine and phenylboronic acid. In addition, pharmaceutical compounds such as milrinone and irbesartan were synthesized via Suzuki-Miyaura coupling using sterically bulky, amido-N-imidazolium salt (4bc) as a ligand. Copyright

A ONE POT PROCESS FOR PREPARING 2-BUTYL-3-[[2'-(1H-TETRAZOL-5-YL)[1,1'-BIPHENYL]-4-YL]METHYL]-1,3-DIAZASPIRO [4, 4] NON-1-EN-4-ONE (IRBESARTAN)

A one pot process for the synthesis of Irbesartan comprising reacting 2-n-Butyl-1, 3-Diazaspiro [4, 4] Non -1-en-4-one (Formula III) and Bromomethyl Cyanobiphenyl (Formula IV) in the presence of base and water with the optional use of PTC to give formula II from which Irbesartan is obtained by reacting with sodium azide and triethylamine hydrochloride in the presence of a non polar solvent.

A new process for the preparation of irbesartan

A process for the preparation of Irbesartan or a pharmaceutically acceptable salt thereof comprising the step of coupling the 1-pentanamidocyclapentanecarboxamide of formula (V) with 4'-substituted methyl biphenyl-2-carbonitrile or 1-(4'-substituted methyl biphenyl-2-yl)-1H-tetrazole wherein tetrazole can be protected or unprotected to obtain the N-[(2'-cyanobiphenyl-4-yl)methyl]-1-pentanamidocyclopentanecarboxamide or N-[1-({[2'-(1H-tetrazol-1-yl)biphenyl-4-yl]methylamino)methyl)cydopentyl]pentanamide wherein tetrazole can be protected or unprotected that is further processed to Irbesartan or a pharmaceutical acceptable salt thereof.

PROCESS FOR PURE IRBESARTAN

The present invention provides an improved and commercially viable process for preparation of irbesartan intermediate, 1-[(2′-cyanobiphenyl-4-yl)methyl]-2-n-butyl-4-spirocyclopentane-2-imidazolin-5-one, substantially free of 1-[(2′-cyanobiphenyl-4-yl)methyl]-2-n-propyl-4-spirocyclopentane-2-imidazolin-5-one impurity, thereby producing irbesartan substantially free of the undesired propyl analog impurity, namely 2-propyl-3-[[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-yl]methyl]-1,3 -diazaspiro[4.4]non-1-en-4-one. The present invention also provides a process for preparation of irbesartan substantially free of tin content. The present invention further provides a commercially viable process for preparation of irbesartan in high purity and in high yield.

PROCESS FOR PURE IRBESARTAN

The present invention provides an improved and commercially viable process for preparation of irbesartan intermediate, 1-[(2''-cyanobiphenyl-4-yl)methyl]-2-n-butyl-4-spirocyclopentane-2-imidazolin-5-one, substantially free of 1-[(2''-cyanobiphenyl-4-yl)methyl]-2-n-propyl-4-spirocyclopentane-2-imidazolin-5-one impurity, thereby producing irbesartan substantially free of the undesired propyl analog impurity, namely 2-propyl-3-[[2''-(1H-tetrazol-5-yl)[1,1''-biphenyl]-4-yl]methyl]-1,3-diazaspiro[4.4]non-1-en-4-one. The present invention also provides a process for preparation of irbesartan substantially free of tin content. The present invention further provides a commercially viable process for preparation of irbesartan in high purity and in high yield.

IMPROVED PROCESS FOR PREPARING IRBESARTAN

Disclosed herein is an improved, commercially viable and industrially advantageous process for the preparation of Irbesartan, or a pharmaceutically acceptable salt thereof, in high yield and purity.

A novel and improved process for the preparation of Irbesartan, an angiotensin-II receptor antagonist for the treatment of hypertension

2-Butyl-3-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1,3-diaza-spiro[4,4]non-1-en-4-one (Irbesartan) is prepared by reacting 1-(2'-cyanobipehnyl-4-yl)methyl)-2-n-butyl-4-spirocyclopentane-2-imidazolin-5-one with sodium azide and zinc halide, in organic solvent.