138402-05-8

Basic information

• Product Name: 2-N-BUTYL-1,3-DIAZA-SPIRO[4,4]NON-1-EN-4-ONE HYDROCHLORIDE
• Synonyms: 2-BUTYL-1,3-DIAZASPIRO[4.4]NON-1-EN-4-ONE HCL;2-BUTYL-1,3-DIAZASPIRO[4,4]NON-1-ENE-4-ONE HYDROCHLORIDE;2-N-BUTYL-1,3-DIAZA-SPIRO[4,4]NON-1-EN-4-ONE HCL;2-N-BUTYL-1,3-DIAZA-SPIRO[4,4]NON-1-EN-4-ONE HYDROCHLORIDE;2-N-BUTYL-1,3-DIAZA-SPIRO[4,4]NON-1-EN-4-ONE MONOHYDROCHLORIDE;2-Butyl-1,3-diazaspiro4.4non-1-en-4-one;2-Butyl-1,3-Diazaspiro[4,4]Non-1-En-4-One Hydrochloride;2-BUTYL-1,3-DIAZASPSPIRO[4,4]NON-1-EN-4-ONE
• CAS NO: 138402-05-8
• Molecular Formula: C₁₁H₁₈N₂O
• Molecular Weight: 194.28
• Product Categories: Heterocyclic Compounds;Heterocycles
• Mol File: 138402-05-8.mol
• Article Data: 15

Chemical Properties

• Boiling Point: 294.7±23.0 °C(Predicted)
• Appearance: oil
• Density: 1.186 g/cm³
• Refractive Index: 1.592
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 6.42±0.20(Predicted)
• CAS DataBase Reference: 2-N-BUTYL-1,3-DIAZA-SPIRO[4,4]NON-1-EN-4-ONE HYDROCHLORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: 2-N-BUTYL-1,3-DIAZA-SPIRO[4,4]NON-1-EN-4-ONE HYDROCHLORIDE(138402-05-8)
• EPA Substance Registry System: 2-N-BUTYL-1,3-DIAZA-SPIRO[4,4]NON-1-EN-4-ONE HYDROCHLORIDE(138402-05-8)

Safety Data

• Hazardous Substances Data: 138402-05-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
2-N-Butyl-1,3-Diazaspiro[4,4]Non-1-En-4-One Hydrochloride is used as a chemical intermediate for the production of Irbesartan (Avapro) (I751000), which is a medication used to treat high blood pressure and type 2 diabetes. Its role in the synthesis process is crucial for the development of this medication, as it contributes to the overall structure and function of the final product.

InChI:InChI=1/C11H18N2O/c1-2-3-6-9-12-10(14)11(13-9)7-4-5-8-11/h2-8H2,1H3,(H,12,13,14)

Upstream product

• 17193-28-1 1-aminocyclopentane-1-carboxamide 
• 177219-40-8 1-(pentanoylamino)cyclopentanecarboxamide 
• 151257-03-3 2-n-butyl-1,3-diazaspiro<4.4>nonan-4-one 
• 638-29-9 n-valeryl chloride 
• 16195-83-8 1-aminocyclopentanecarbonitrile hydrochloride 
• 253269-07-7 (N-valeryl)-1-aminocyclopentanecarboxamide 
• 1664-35-3 ethyl 1-aminocyclopentanecarboxylate 
• 999-09-7 ethyl valerimidate 
• 931-17-9 1,2-Cyclohexanediol 
• 18257-46-0 pentanamidine hydrochloride 
• 4524-93-0 Cyclopentanecarboxylic acid chloride 

Downstream Products

• 1029083-94-0 irbesartan trifluoroacetate 
• 960004-52-8 C₁₈H₂₃N₃O₃ 
• 1255948-69-6 2-(4-((2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl)-2-ethoxymethylphenyl)benzenesulfonic acid 
• 948349-73-3 3-[4-(2-butyl-4-oxo-1,3-diaza-spiro[4.4]non-1-en-3-yl-methyl)-2-ethoxymethyl-phenyl]-5-methyl-thiophene-2-sulphonic acid (4,5-dimethyl-isoxazol-3-yl)-(2-methoxy-ethoxymethyl)-amide 
• 1003960-86-8 2-butyl-1-[(3'-(cyanomethoxy)biphenyl-4-yl)methyl]-4-spirocyclopentyl-1H-imidazol-5(4H)-one 
• 1003960-11-9 2-butyl-1-[(3'-((1-ethoxycarbonyl-1,1-dimethylmethyl)oxy)biphenyl-4-yl)methyl]-4-spirocyclopentyl-1H-imidazol-5(4H)-one 
• 1003960-12-0 1-[(6'-bromo-3'-((1-ethoxycarbonyl-1,1-dimethylmethyl)oxy)biphenyl-4-yl)methyl]-2-butyl-4-spirocyclopentyl-1H-imidazol-5(4H)-one 
• 138401-24-8 4'-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-[1,1'-biphenyl]-2-carbonitrile 

Relevant articles and documents

OMS-2 nanorod-supported cobalt catalyst for aerobic dehydrocyclization of vicinal diols and amidines: Access to functionalized imidazolones

The development of reusable base metal catalysts for innovative catalytic transformations is a key technology toward sustainable production of fine chemicals, pharmaceuticals, and other function products. Herein, we report the preparation of a new highly dipersed manganese oxides of octahedral molecular sieve (OMS-2) nanorod-supported cobalt catalyst, which is successfully applied for aerobic dehydrocyclization of vicinal diols and amidines to access structurally diverse imidazolones, a class of valuable compounds found in numerous natural and biomedical products. The developed catalytic transformation proceeds with broad substrate scope, good functional group compability, the use of green molecular oxygen and reusable cobalt catalyst, which offers an important platform for the conversion of abundant and sustainable alcohol resources into functional N-heterocycles. The strategy combining nanocatalyst design with aerobic dehydrocoupling is anticipated to achieve other challenging catalytic transformations.

Discovery of Irbesartan Derivatives as BLT2 Agonists by Virtual Screening

Leuktriene B4 receptor 2 (BLT2) is a G-protein coupled receptor modulation of which is discussed to be a therapeutic option for healing of intestinal lesions. In this work, new BLT2 agonists were identified by a virtual screening of a repurposing library and in vitro assay of the most promising compounds. Irbesartan, an approved type-1 angiotensin II receptor (AT1) antagonist, was identified as a moderate BLT2 agonist. An initial SAR study on the irbesartan scaffold was performed resulting in the discovery of a new potent BLT2 agonist (8f, EC50 = 67.6 nM). Irbesartan and 8f were shown to promote proliferation of epithelial colon cells, an effect which was reversible by a BLT2 antagonist.

Synthesis of 2-Aminoimidazolones and Imidazolones by (3 + 2) Annulation of Azaoxyallyl Cations

The first examples of (3 + 2) annulations between azaoxyallyl cations and cyanamides and nitriles to give the corresponding 2-aminoimidazolones and imidazolones are reported. On the basis of the isolation of unexpected imidate products with certain substr

Design, synthesis and evaluation of novel potent angiotensin II receptor 1 antagonists

A series of new angiotensin II (Ang II) receptor 1 antagonists were designed, synthesized and evaluated. All compounds showed nanomolar affinities for the angiotensin II type 1 receptor in radioligand binding assays and could reduce blood pressure signifi

Oxidation of substituted imidazolidin-4-ones: New alternative method preparation of 4,5-dihydro-1H-imidazol-5-ones

The reaction of aldehydes (pentanal, benzaldehyde, 4-methoxybenzaldehyde, 4-nitrobenzaldehyde, salicylaldehyde, pyridin-2-carbaldehyde) with 1-aminocyclopentancarboxamide or (S)-2-amino-2,3-dimethylbutanamide has been used to prepare substituted imidazolidin-4-ones 1a-g (a: R1 = CH 3(CH2)3; b: R1 = C6H 5; c: R1 = 4-CH3OC6H4; d: R1 = 4-NO2C6H4; e: R1 = 2-HOC6H4; f: R1 = 2-pyridyl; for R2 = R3 = (CH2)4), and g: R1 = 2-pyridyl; for R2 = CH3; R3 = CH(CH 3)2) in the yields of 53-83%. Subsequent oxidations with various reagents gave the corresponding 4,5-dihydro-1H-imidazol-5-ones 2a-g: Pd/C (72-93%), DDQ (25-80%), and MnO2 (30-77%). Structure of the prepared compounds 1a-g and 2a-g was verified by 1H NMR and 13C NMR spectroscopy, EI-MS and elemental analysis. X-ray diffraction was performed in the case of compounds 1e and 2e.

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.

SUBSTITUTED IMIDAZOLONE DERIVATIVES, PREPARATIONS AND USES

The present invention relates to polysubstituted imidazolone derivatives, to the pharmaceutical compositions comprising them and to the therapeutic uses thereof in the human and animal health fields. The present invention also relates to a process for preparing these derivatives.

Process for the preparation of 2-alkyl-1-((2'-substituted-biphenyl-4-yl) Methyl)-imidazole, dihydroimidazole or benzimidazloe derivatives

The invention relates to a new process for the preparation of sartans 2-butyl-3-[[2′-[1-(triphenylmethyl)-1H-tetrazol-5-yl][1,1′-biphenyl]-4-yl]methyl]-1,3-diazaspiro[4.4]non-1-en-4-one is disclosed, which proceeds via novel intermediate, 4-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]phenylboronic acid (Formula (II)) or its analogs. Compound (II) reacts with 5-(2-bromophenyl)-1-(triphenylmethyl)-1H-tetrazole (III) in the presence of catalyst, using conditions of Suzuki reaction, to give trityl irbesartan (I), whereas analogs to compound (II) may give candesartan, valsartan, telmisartan, losartan and olmesartan.

Original loading and Suzuki conditions for the solid-phase synthesis of biphenyltetrazoles. Application to the first solid-phase synthesis of irbesartan

Biphenyltetrazoles are recognized privileged structures. Among them, the therapeutically important class of sartans displays antagonistic activity on AT1 receptors. We have developed a method for anchoring tetrazole derivatives via the heterocycle on a hydroxylated resin using zinc triflate. New Suzuki-Miyaura cross-coupling conditions are developed for the quantitative formation of the phenyl-phenyl bond. Our straightforward synthesis scheme, starting from the conserved phenyltetrazole moiety and ending with the appending of the structurally variable moiety, is well suited to the preparation of sartans and their analogues at a laboratory scale. We thus describe here the first solid phase synthesis of irbesartan, a marketed AT1 antagonist.

Synthesis and screening for acetylcholinesterase inhibitor activity of some novel 2-butyl-1,3-diaza-spiro[4,4]non-1-en-4-ones: Derivatives of irbesartan key intermediate

The association of bioactive nucleus with other pharmacological agents is hoped to improve the efficacy of the treatment by combining the effects of different pharmacological mechanisms of action. Keeping this in view, a series of 2-butyl-1,3-diaza-spiro[4,4]non-1-en-4-one derivatives have been synthesized by interaction of 2-butyl-1,3-diaza-spiro[4,4]non-1-en-4-one with different bioactive aralkyl halides in presence of powdered potassium carbonate by two different methods viz., conventional and microwave irradiation. The yields under conventional and microwave irradiation methods were in the range of 60-65% and 80-90%, respectively. The structure elucidation of the new compounds has been carried out with the help of elemental analysis and spectral data. All the synthesized compounds have been screened for their efficacy as acetylcholinesterase (AChE) inhibitor. AChE inhibitory activity study was carried out by using Ellman colorimetric assay with neostigmine as a reference standard against targets from different species, such as pure electric eel AChE, human serum AChE, and rat brain AChE. Among the compounds synthesized, compounds 5a, 5b, 5j showed good inhibition against AChE.