521284-22-0

Basic information

• Product Name: (alphaR)-alpha-[[[2-(4-Aminophenyl)ethyl]amino]methyl]benzenemethanol hydrochloride
• Synonyms: (alphaR)-alpha-[[[2-(4-Aminophenyl)ethyl]amino]methyl]benzenemethanol hydrochloride;(R)-alpha-[[[2-(4-AMinophenyl)ethyl]aMino]Methyl];(R)-[[[2-(4-aMinophenyl)ethyl]aMino]Methyl]- BenzeneMethanol HCl;(R)-2-((4-AMinophenethyl)aMino)-1-phenylethanol hydrochloride;(R)--[[[2-(4-aminophenyl)ethyl]amino]methyl]-Benzenemethanol;Mirabegron INT 3;(R) -2 - [[2- (4- aminophenyl) ethyl] amino] -1-phenylethanol hydrochloride;(1R)-2-{[2-(4-Aminophenyl)ethyl]amino}-1-phenylethanol hydrochlor ide (1:1)
• CAS NO: 521284-22-0
• Molecular Formula: C₁₆H₂₀N₂O*ClH
• Molecular Weight: 292.80374
• EINECS: 1592732-453-0
• Mol File: 521284-22-0.mol

Chemical Properties

• Appearance: /
• Density: 1145 at 20℃
• Vapor Pressure: 0.015Pa at 25℃
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• CAS DataBase Reference: (alphaR)-alpha-[[[2-(4-Aminophenyl)ethyl]amino]methyl]benzenemethanol hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: (alphaR)-alpha-[[[2-(4-Aminophenyl)ethyl]amino]methyl]benzenemethanol hydrochloride(521284-22-0)
• EPA Substance Registry System: (alphaR)-alpha-[[[2-(4-Aminophenyl)ethyl]amino]methyl]benzenemethanol hydrochloride(521284-22-0)

Safety Data

• Hazardous Substances Data: 521284-22-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(alphaR)-alpha-[[[2-(4-Aminophenyl)ethyl]amino]methyl]benzenemethanol hydrochloride is used as a pharmaceutical intermediate for the development of various drugs. Its unique structure and functional groups make it a valuable component in the synthesis of new therapeutic agents, potentially targeting a wide range of medical conditions.
Used in Organic Synthesis:
In the field of organic chemistry, (alphaR)-alpha-[[[2-(4-Aminophenyl)ethyl]amino]methyl]benzenemethanol hydrochloride serves as an organic synthesis intermediate. It can be employed in the creation of more complex organic molecules, which may have applications in various industries, including pharmaceuticals, agrochemicals, and materials science.
Used in Laboratory Research and Development:
(alphaR)-alpha-[[[2-(4-Aminophenyl)ethyl]amino]methyl]benzenemethanol hydrochloride is also used in laboratory research and development processes, where it can be further modified or studied to understand its properties and potential applications. Researchers may use it to explore new reaction pathways, develop novel synthetic methods, or investigate its biological activities.
Used in Chemical Production Processes:
(alphaR)-alpha-[[[2-(4-Aminophenyl)ethyl]amino]methyl]benzenemethanol hydrochloride is utilized in chemical production processes, where it may be scaled up for the synthesis of larger quantities of the compound or its derivatives. This can be particularly important for the commercialization of new drugs or the development of new materials with specific properties.

Synthesis

A mixture of (100 g) (R)-2-[2’ -(4-nitrophenyl)ethyl]amino] -1 -phenylethanol monohydroch bride (prepared according to example Ib), methanol (2000 mL) and Raney Nickel (20 g, wet) was stirred under hydrogen pressure (60 psi) for 6 hrs. The reaction solution was filtered, and the filtrate was concentrated in vacuo. The residue was mixed with isopropanol (300 mL) and reaction mixture was heated to 78°C (±2). The mixture was added to toluene (900 mL). The reaction mixture was gradually cooled to 28°C (±2) and stirred at this temperature for 3 hrs. The solid obtained was filtered, washed with toluene and dried under vacuo at 48°C (±2) to obtain (R)-2-[[2-(4-aminophenyl)ethyl]-amino]- I -phenylethanol monohydrochioride.Yield: 78.1 g (86.1%); Purity by HPLC: 99.14 %.

InChI:InChI=1S/C16H20N2O.ClH/c17-15-8-6-13(7-9-15)10-11-18-12-16(19)14-4-2-1-3-5-14;/h1-9,16,18-19H,10-12,17H2;1H/t16-;/m0./s1

Upstream product

• 521284-21-9 (R)-2-[[2′-(4-nitrophenyl)ethyl]amino]-1-phenylethanol hydrochloride 
• 29968-78-3 2-(4-nitrophenyl)ethylamine monohydrochloride 
• 611-71-2 (R)-Mandelic Acid 
• 521284-19-5 (2R)-2-hydroxy-N-[2-(4-nitrophenyl)ethyl]-2-phenylethanamide 

Downstream Products

• 223673-61-8 (R)-2-(2-aminothiazol-4-yl)-4'-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetanilide 

Relevant articles and documents

A new process for the preparation of (R)-2-((4-Aminophenethyl)amino)-1-phenylethanol

The present invention relates to a process for the preparation (R)-2 - ((4-aminophenethyl) amino) -1 - phenylethanol, which is an intermediate of mirabberone intermediate. A manufacturing method of a high purity and high yield amide derivative is provided to produce an amide derivative having high purity and high yield without using a specific purification process by using a zinc powder reduction catalyst.

Systematic Investigation into the Formation of Significant Amounts of Unknown Impurity during Scale-up of NaBH4-I2 Mediated Reduction of Nitro-Amide Intermediate of Mirabegron No.

After successful development of a manufacturing process for the Mirabegron (1) at the laboratory scale, a muddled situation was aroused during the scale-up batches, wherein sodium borohydride-iodine (NaBH4-I2) mediated reduction of nitro-amide 4 ended up with substantial amounts (～10%) of unspecified impurity in the nitro-amine intermediate 5. On the basis of the structure elucidation and meticulous investigation, a reaction path for its genesis during the process was identified and an efficient mechanism proposed to arrest its formation. In-situ generated nickel boride (Ni2B) due to reaction of NiI2 (corrosion product) with NaBH4 followed by electrophilic attack of THF (solvent) was found to be the reason for the formation of impurity (8a). Execution of subsequent batches with proper controls arrested this impurity and successfully provided the Mirabegron with the desired quality.

A PROCESS FOR PREPARATION OF MIRABEGRON AND ALPHA CRYSTALLINE FORM THEREOF

An improved process for the preparation of Mirabegron of formula (I) where 4- nitrophenylethylamine of formula (III) or its acid addition salt of formula (IlIa) reacted with compound of formula (XII) in a solvent, optionally in presence of base and/or catalyst to obtain (R)-2-hydroxy-N-[2-(4-nitrophenyl)ethyl]-2-phenylacetamide of formula (XIII) followed by reducing (R)-2-hydroxy-N-[2-(4-nitrophenyl)ethyl]-2-phenylacetamide of formula (XIII) in a solvent to obtain (R)-2-[2'-(4-nitrophenyl)ethyl]amino]-l-phenylethanol of formula (XIV), optionally converting it into its acid addition salt of formula (XlVa); reducing (R)-2-[2'-(4- nitrophenyl)ethyl]amino]-l -phenylethanol of formula (XIV) or its acid addition salt of formula (XlVa) further in solvent to obtain (R)-2-[[2-(4-aminophenyl)ethyl]-amino]-l -phenylethanol of formula (XV) or its acid addition salt of formula (XVa) respectively; and reacting compound (R)- 2-[[2-(4-aminophenyl)ethyl]-amino]-l-phenylethanol of formula (XV) or its acid addition salt of compound of formula (XVa) with compound of formula (VII) in solvent, optionally in the presence of acid, and/or a catalyst to obtain Mirabegron of formula (I) which is further isolated as its a- crystalline form. The compound of formula (XIV) used in the foregoing process can also be prepared by reacting with a compound of formula (III) or acid addition salt of compound of formula (IlIa) in presence of a solvent, a catalyst and optionally in presence of a base to obtain compound of formula (XIV) optionally converting it into its acid addition salt of formula (XlVa); and the same is used in the above-referred process. The compound of formula (XV) used in the foregoing process can also be prepared by reacting a compound of formula (III) or its acid addition salt of formula (IlIa) with a compound of formula (XVI) in a solvent, optionally in presence of a base, optionally in presence of a catalyst to obtain compound of formula (XVII); and optionally isolate the compound of formula (XVII) followed by reducing the compound of formula (XVII) using reducing agent, in a solvent, optionally in presence of a base, optionally in presence of a catalyst to obtain compound of formula (XV) which is further used in the above- referred process for the preparation of Mirabegron of formula (I) and its a-crystalline form. Another additional single-pot process for preparation of Mirabegron of formula (I) is disclosed, wherein compound of formula (XV) or its acid addition salt of formula (XVa) reacted with compound of formula (XVIII) in presence of a solvent and oxidizing agent, optionally in presence of base, optionally in presence of a catalyst to obtain Mirabegron of formula (I).

AN IMPROVED PROCESS FOR THE PREPARATION OF 2-(2-AMINOTHIAZOL-4-YL)-N-[4-(2-[[(2R)-2-HYDROXY-2- PHENYLETHYL]AMINO]-ETHYL)PHENYL]ACETAMIDE

The present invention relates to an improved process for the preparation of pure 2-(2- amino-1,3-thiazol-4-yl)-N-[4-(2-[(2R)-2-hydroxy-2-phenylethyl]amino]ethylphenyl]- acetamide of formula (1) substantially free of impurities. The present invention relates to the novel process of preparing intermediate (R)-1- Phenyl-2-[[2-(4-nitrophenyl)ethyl]amino]ethanol hydrochloride of formula (2) in high yield, which is useful in the preparation of mirabegron of formula (1). The process also relates to the preparation of pure α –form crystal of 2-(2-Amino- 1,3-thiazol-4-yl)-N-[4-(2-[(2R)-2-hydroxy-2-phenylethyl]amino]ethylphenyl]acetamide Mirabegron (1) without isolation of β-form.

PROCESS FOR THE PREPARATION OF 2-(2-AMINOTHIAZOL-4-YL)-N-[4-(2-{[(2R)-2-HYDROXY-2-PHENYL ETHYL]AMINO}ETHYL)PHENYL]ACETAMIDE MONOHYDROCHLORIDE, ITS INTERMEDIATES AND POLYMORPH THEREOF

The present invention relates to a process for the preparation of 2-(2-aminothiazol-4-yl)- N-[4-(2- {[(2R)-2-hydroxy-2-phenylethyl]amino} ethyl)phenyl]acetamide monohydrochloride compound of formula- la, its intermediates and polymorph thereof. [Formula should be inserted here]

REMEDY FOR OVERACTIVE BLADDER COMPRISING ACETIC ACID ANILIDE DERIVATIVE AS THE ACTIVE INGREDIENT

(R)-2-(2-aminothiazol-4-yl)-4'-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetic acid anilide or its salt shows a potent bladder relaxation effect in "isolated rat bladder smooth muscle relaxation test", dose-dependently lowers the contraction frequency of rhythmic bladder contractions in "rat rhythmic bladder contraction measurement test" and, moreover, prolongs the urination intervals in "urination functions measurement test on cyclophosphamide-induced overactive bladder model rat". Owing to these effects, the above compound is useful as a remedy for ovaractive bladder.

ALPHA-FORM OR BETA-FORM CRYSTAL OF ACETANILIDE DERIVATIVE

To provide novel crystals useful as an ingredient for the production of a diabetes remedy. The invention is concerned with α-form crystal and β-form crystal of (R)-2-(2-aminothiazol-4-yl)-4'-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetanilide. The α-form crystal does not exhibit hygroscopicity and has stability such that it can be used as a medicine, and is useful for mass synthesis in the industrial production. The β-form crystal does not relatively exhibit hygroscopicity and is also useful as a production intermediate of the α-form crystal.