521284-21-9

Basic information

• Product Name: (R)-2-((4-Nitrophenethyl)amino)-1-phenylethanol hydrochloride
• Synonyms: (R)-2-[[2-(4-nitrophenyl ethyl] aMino]-1-phenyl ethanol Monohydrochloride;(alphaR)-alpha-[[[2-(4-Nitrophenyl)ethyl]aMino]Methyl]benzeneMethanol hydrochloride;(R)-2-((4-Nitrophenethyl)aMino)-1-phenylethanol hydrochloride;(R)-2-[2-(4-Nitro-phenyl)-ethylamino]-1-phenyl-ethanol Hydrochloride;R-2-((4-nitrophenethyl)amino)-1-phenylethan-1-ol hydrochloride;(1R)-2-[2-(4-nitrophenyl)ethylamino]-1-phenylethanol,hydrochloride;(R)-2-(4-nitrophenethylamino)-1-phenylethanol monohydrochloride;5-METHYL-3-PYRROLIDONE
• CAS NO: 521284-21-9
• Molecular Formula: C₁₆H₁₈N₂O₃*ClH
• Molecular Weight: 286.32572
• EINECS: -0
• Product Categories: CMLLYL
• Mol File: 521284-21-9.mol

Chemical Properties

• Appearance: /
• Storage Temp.: Inert atmosphere,Room Temperature
• Solubility: DMSO (Slightly), Water (Slightly)
• CAS DataBase Reference: (R)-2-((4-Nitrophenethyl)amino)-1-phenylethanol hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-2-((4-Nitrophenethyl)amino)-1-phenylethanol hydrochloride(521284-21-9)
• EPA Substance Registry System: (R)-2-((4-Nitrophenethyl)amino)-1-phenylethanol hydrochloride(521284-21-9)

Safety Data

• Hazardous Substances Data: 521284-21-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(R)-2-((4-Nitrophenethyl)amino)-1-phenylethanol hydrochloride is used as a synthetic intermediate for the preparation of (aminothiazolyl)acetanilide derivatives. These derivatives are of interest in the development of new treatments for diabetes, as they may help regulate blood sugar levels and improve the management of the disease.
Additionally, this compound could potentially be used in other applications within the pharmaceutical industry, such as the synthesis of other therapeutic agents or as a building block for more complex molecular structures with specific biological activities. However, further research and development would be required to explore these possibilities and validate their efficacy and safety.

Upstream product

• 521284-19-5 (2R)-2-hydroxy-N-[2-(4-nitrophenyl)ethyl]-2-phenylethanamide 
• 20780-53-4 (R)-Styrene oxide 
• 29968-78-3 2-(4-nitrophenyl)ethylamine monohydrochloride 
• 24954-67-4 2-(p-nitrophenyl)ethylamine 
• 40434-87-5 (R)-2-hydroxy-2-phenylethyl 4-methylbenzenesulfonate 
• 611-71-2 (R)-Mandelic Acid 
• 70-11-1 α-bromoacetophenone 
• 223673-34-5 (R)-2-(4-nitrophenylethylamino)-1-phenylethan-1-ol hydrochloride 
• 56751-12-3 2-chloro-1-phenylethanol 

Downstream Products

• 521284-22-0 (R)-2-[ [2-(4-aminophenyl)ethyl]-amino]-1-phenylethanol monohydrochloride 
• 391901-45-4 YM-208876 
• 223673-35-6 ((2R)-2-hydroxy-2-phenylethyl)-[2-(4-nitrophenyl)ethyl]carbamic acid tert-butyl ester 
• 223673-36-7 (R)-(4-aminophenylethyl)(2-hydroxy-2-phenylethyl)carbamic acid tert-butyl ester 

Relevant articles and documents

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.

Synthetic method (1R)-2-[[[2-(4-nitrophenyl) ethyl] amino] methyl] phenylmethylamine hydrochloride

The reaction is mild and the (1R) - 2 - [[[2 - (4 - operation) is] easy]] to obtain-nitrophenyl ethyl, amino methyl :S1,methyl,1R - 2-benzyl alcohol, hydrochloride, the reaction is mild and ;S2, the operation is simple 60-65 °C, and, the 1-48h, method ;S3, comprises the following steps: stirring the mixture solution to. The reaction mixture, is stirred and]] refluxed (1R) - 2 - [[[2 - (4 -) at, room] temperature S1 1R - 2 and stirred at reflux 1:1-20, temperature. S1 The reaction solution is cooled and is 25%-28%, stirred and 1R - 2 refluxing under 1-1.5 DEG. C by adding a solvent and a solvent in step to a reaction solution at a temperature of. The method comprises the following steps of: Step, carrying out clean production by reaction. The, reaction, solution is, added with a solvent and, a solvent. and a solvent and a solvent in a reaction solution at room temperature in a reaction solution is stirred at a temperature in a range from about times .10 10 1-phenoxyethyl-phenyl-methyl-methyl-methyl-phenyl-ethanolate.

Synthesis of mirabegron intermediate (R)-2-(4-nitrophenethylamino)-1-phenylethanol hydrochloride

The invention discloses synthesis of a mirabegron intermediate (R)-2-(4-nitrophenethylamino)-1-phenylethanol hydrochloride. The synthesis comprises the following steps: firstly, enabling alpha-bromoacetophenone and 4-nitro-phenethylamine to react in a solvent in the presence of alkali to generate an intermediate I; then carrying out reduction reaction on the intermediate I under the action of a chiral inducing agent and a reducing agent to generate an intermediate II; enabling the intermediate II to react with concentrated hydrochloric acid in a solvent to generate a target product. Accordingto the synthesis method disclosed by the invention, EDCI (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide), HOBt (Hydroxybenzotriazole) and DMI (1,3-dimethyl-2-imidazolidinone) which have a relatively high price, and hypertoxic R-styrene oxide can be avoided; the synthesis method has the advantages of easiness for obtaining raw materials, low cost, simplicity in operation and few impurities and is suitable for industrial production.

Preparation and application of (R)-2-[[2-(4-aminophenyl)ethyl]amino]-1-phenylethyl alcohol

The invention provides an intermediate, (R)-2-[[2-(4-aminophenyl)ethyl]amino]-1-phenylethyl alcohol, of mirabegron, and a synthetic method and application of the intermediate, and belongs to the technical field of pharmaceutical synthesis. The structural formula of (R)-2-[[2-(4-aminophenyl)ethyl]amino]-1-phenylethyl alcohol is shown in the description. A synthetic step comprises: reducing (R)-2-[[2-(4-nitrophenyl)ethyl]amino]-1-phenylethyl alcohol monohydrochloride (I) into (R)-2-[[2-(4-aminophenyl)ethyl]amino]-1-phenylethyl alcohol (II) in the presence of an alcohol solvent through taking Pd/C as a catalyst and using a phase-transfer reagent. The synthetic method is mild in reaction condition and simple to operate. What's more, an organic compound instead of hydrogen is taken as a hydrogen donor during reaction, thereby overcoming technique, equipment, and safety problems due to usage of hydrogen. The synthetic method is extremely beneficial for industrial production.

Synthetic method of mirabegron intermediate

The invention discloses a synthetic method of a mirabegron intermediate (R)-2-(4-nitrobenzene ethyl amino)-1-phenyl ethanol hydrochloride (M-02) and belongs to the field of drug synthesis. The method comprises steps as follows: (1) R-mandelic acid and pivaloyl chloride produce a mixed anhydride intermediate (I); (2) the mixed anhydride intermediate (I) and 4-nitrobenzene ethylamine are subjected to an acrylation reaction to produce an intermediate (II); (3) a mirabegron intermediate (M-01) is obtained through hydrolysis of the intermediate (II); (4) an amido bond of the intermediate (M-01) is reduced and the mirabegron intermediate (M-02) is obtained. The reaction condition is mild, the yield is high, few impurities exist, the production cost is low, and the method is suitable for mass industrial production.

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.

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).

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.