743460-48-2

Basic information

• Product Name: biphenyl-2-ylcarbamic acid 1-[2-(methylamino)ethyl]piperidin-4-yl ester
• Synonyms: biphenyl-2-ylcarbamic acid 1-[2-(methylamino)ethyl]piperidin-4-yl ester
• CAS NO: 743460-48-2
• Molecular Weight: 353.464
• Mol File: 743460-48-2.mol

Chemical Properties

• Boiling Point: 477.2±45.0 °C(Predicted)
• Density: 1.16±0.1 g/cm3(Predicted)
• CAS DataBase Reference: biphenyl-2-ylcarbamic acid 1-[2-(methylamino)ethyl]piperidin-4-yl ester(CAS DataBase Reference)
• NIST Chemistry Reference: biphenyl-2-ylcarbamic acid 1-[2-(methylamino)ethyl]piperidin-4-yl ester(743460-48-2)
• EPA Substance Registry System: biphenyl-2-ylcarbamic acid 1-[2-(methylamino)ethyl]piperidin-4-yl ester(743460-48-2)

Safety Data

• Hazardous Substances Data: 743460-48-2(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Biphenyl-2-ylcarbamic acid 1-[2-(methylamino)ethyl]piperidin-4-yl ester is used as an active pharmaceutical ingredient (API) for the development of revefenacin and its salts. It is specifically utilized for the treatment of chronic obstructive pulmonary disease (COPD), a group of lung diseases that cause airflow blockage and breathing-related problems. As a LAMA, revefenacin helps to reduce symptoms such as shortness of breath, wheezing, and coughing by relaxing the airway muscles and improving lung function.
Additionally, revefenacin may be used in combination with other medications, such as long-acting beta2-agonists (LABAs), to provide a dual bronchodilator therapy for patients with moderate to severe COPD. This combination can offer enhanced symptom relief and improved lung function compared to monotherapy.

Upstream product

• 32315-92-7 N-methyl-2-chloroethylamine 
• 171722-92-2 4-piperidyl N-(2-biphenyl)carbamate 
• 40052-63-9 1-bromo-2-(N-methylamino)ethane hydrobromide 
• 4535-90-4 N-methyl-2-chloroethylamine hydrochloride 
• 171723-80-1 1-benzyl-4-piperidylbiphenyl-2-ylcarbamate 
• 17337-13-2 [1,1'-biphenyl]-2-yl-isocyanate 
• 4727-72-4 1-benzyl-4-hydroxypiperidine 
• 864686-28-2 biphenyl-2-yl-carbamic acid 1-[2-(benzylmethylamino)ethyl]piperidin-4-yl ester 
• 743460-49-3 biphenyl-2-ylcarbamic acid 1-[2-((benzyloxycarbonyl)-N-methylamino)ethyl]piperidin-4-yl ester 
• 107201-33-2 N-<(benzyloxy)carbonyl>-N-methylaminoacetaldehyde 

Downstream Products

• 864751-39-3 N-{2-[4-(Biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]ethyl}-2,5-dibromo-N-methylterephthalamic Acid 
• 864751-45-1 N-{2-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]ethyl}-3-methoxy-n-methylterephthalamic acid methyl ester 
• 864760-28-1 biphenyl-2-yl-carbamic acid 1-{2-[(4-formylbenzoyl)methylamino]ethyl}piperidin-4-yl ester 
• 1246248-31-6 1-{2-[{6-[(4-{4-[(tert-butoxycarbonyl)(methyl)amino]butanoyl}phenyl)amino]hexanoyl}(methyl)amino]ethyl}piperidin-4-yl biphenyl-2-ylcarbamate 
• 1246247-32-4 1-{2-[{3-[2-({4-[{3-[(tert-butoxycarbonyl)(methyl)amino]propyl}(methyl)carbamoyl]phenyl}amino)ethoxy]propanoyl}(methyl)amino]ethyl}piperidin-4-yl biphenyl-2-ylcarbamate 
• 1246247-23-3 C₃₂H₄₉N₃O₅Si 
• 1246247-05-1 tert-Butyl 4-({6-[(2-{4-[(biphenyl-2-ylcarbamoyl)oxy]piperidin-1-yl}ethyl)(methyl)amino]-6-oxohexyl}amino)benzoate 
• 1246248-54-3 ethyl [2-({6-[(2-{4-[(biphenyl-2-ylcarbamoyl)oxy]piperidin-1-yl}ethyl)(methyl)amino]-6-oxohexyl}amino)-1,3-thiazole-4-yl]acetate 
• 1246248-34-9 1-{2-[{6-[(4-{4-[(tert-butoxycarbonyl)(methyl)amino]butanoyl}benzyl)(methyl)amino]hexanoyl}(methyl)amino]ethyl}piperidin-4-yl biphenyl-2-ylcarbamate 
• 1246246-97-8 C₄₄H₆₁FN₆O₆ 
• 1246247-68-6 tert-Butyl 3-[{6-[(2-{4-[(biphenyl-2-ylcarbamoyl)oxy]piperidin-1-yl}ethyl)(methyl)amino]-6-oxohexyl}(methyl)amino]benzoate 
• 1246247-67-5 3-({6-[(2-{4-[(Biphenyl-2-ylcarbamoyl)oxy]piperidin-1-yl}ethyl)(methyl)amino]-6-oxohexyl}amino)benzoic acid 
• 1246247-66-4 tert-Butyl 3-({6-[(2-{4-[(biphenyl-2-ylcarbamoyl)oxy]piperidin-1-yl}ethyl)(methyl)amino]-6-oxohexyl}amino)benzoate 
• 1246260-32-1 tert-Butyl 4-({6-[(2-{4-[(biphenyl-2-ylcarbamoyl)oxy]piperidin-1-yl}ethyl)(methyl)amino]-6-oxohexyl}amino)-2-methylbenzoate 

Relevant articles and documents

Preparation method of remifenfloxacin intermediate

The invention discloses a preparation method of a remifenfloxacin intermediate, belongs to the technical field of drug synthesis, and solves the problems of long synthesis route, environmental unfriendliness, harsh reaction conditions and low yield of a remifenfloxacin key intermediate in the prior art. The preparation method of the remifenfloxacin intermediate as shown in the formula I comprises the following steps: reacting a compound as shown in a formula II with a compound as shown in a formula III or a salt thereof to generate a compound as shown in the formula I; the reaction formula is shown in the specification; and wherein X is halogen. The method is simple, easy and convenient to operate, short in route, high in yield, free of toxic oxidizing agents and catalytic hydrogenation, environmentally friendly and easier to industrialize, and only one step is needed.

Preparation method of revefenacin intermediate

The invention discloses a preparation method of a revefenacin intermediate. The preparation method comprises the following steps: (1) carrying out a protective reaction on methylaminoacetaldehyde dimethyl acetal as shown in a formula I and a protecting gr

Preparation methods of revefenacin intermediate and revefenacin

The invention relates to a synthesis method of a revefenacin intermediate, which specifically comprises the following steps: in a solvent, enabling piperidin-4-yl [1,1-biphenyl]-2-carbamate to react with methyl(2-oxyethyl) tert-butyl carbamate in the pres

Discovery of (R)-1-(3-((2-Chloro-4-(((2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)amino)methyl)-5-methoxyphenyl)amino)-3-oxopropyl)piperidin-4-yl [1,1′-biphenyl]-2-ylcarbamate (TD-5959, GSK961081, Batefenterol): First-in-Class dual pharmacology multivalent muscarinic antagonist and β2 agonist (MABA) for the treatment of chronic obstructive pulmonary disease (COPD)

Through application of our multivalent approach to drug discovery we previously reported the first discovery of dual pharmacology MABA bronchodilators, exemplified by 1. Herein we describe the subsequent lead optimization of both muscarinic antagonist and β2 agonist activities, through modification of the linker motif, to achieve 24 h duration of action in a guinea pig bronchoprotection model. Concomitantly we targeted high lung selectivities, low systemic exposures and identified crystalline forms suitable for inhalation devices. This article culminates with the discovery of our first clinical candidate 12f (TD-5959, GSK961081, batefenterol). In a phase 2b trial, batefenterol produced statistical and clinically significant differences compared to placebo and numerically greater improvements in the primary end point of trough FEV1 compared to salmeterol after 4 weeks of dosing in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

PROCESS FOR PREPARING A BIPHENYL-2-YLCARBAMIC ACID

The invention provides a process of preparing an intermediate useful in the synthesis of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester, and a process of preparing a crystalline freebase of the ester.

Crystalline forms of a biphenyl compound

The invention provides crystalline forms of biphenyl-2-ylcarbamic acid 1-[2-({3-[2-(4-hydroxybenzylamino)ethylcarbamoyl]benzoyl}methylamino)ethyl]piperidin-4-yl ester, and pharmaceutically acceptable solvates thereof. The crystalline form can be a freebase (Form I or II), a salt such as a hemiedisylate salt or a heminapadisylate salt, or a solvate of a salt such as a heminapadisylate methanolate or a heminapadisylate ethanolate. The invention also provides pharmaceutical compositions comprising these crystalline compounds or prepared using these compounds; processes and intermediates for preparing the crystalline compounds; and methods of using these compounds to treat a pulmonary disorder.

Biphenyl compounds useful as muscarinic receptor antagonists

The invention provides compounds of formula I: wherein a, b, c, d, n, R1, R2, R3, R6, R7, W, and A are as defined in the specification. The compounds of formula I are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat pulmonary disorders.

Biphenyl compounds useful as muscarinic receptor antagonists

The invention provides compounds of formula I: wherein a, b, c, p, W, A, X1, R1, R2, R3, R6, R7, and R8 are as defined in the specification. The compounds of formula I are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat pulmonary disorders.

Biphenyl compounds useful as muscarinic receptor antagonists

The invention provides compounds of formula I: wherein a, b, c, m, n, q, r, W, Z1, Ar1, Z2, Y, R1, R2, and R3 are as defined in the specification. The compounds of formula I are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat pulmonary disorders.

CRYSTALLINE FORMS OF A BIPHENYL COMPOUND

The invention provides crystalline forms of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester, and pharmaceutically acceptable solvates thereof. The crystalline form can be a freebase, or a salt such as a diphosphate, monosulfate or dioxalate salt. The invention also provides pharmaceutical compositions comprising these crystalline compounds or prepared using these compounds; processes and intermediates for preparing the crystalline compounds; and methods of using these compounds to treat a pulmonary disorder.