521284-19-5

Usage

Uses

Used in Pharmaceutical Industry:
(alphaR)-alpha-Hydroxy-N-[2-(4-nitrophenyl)ethyl]benzeneacetamide is used as a pharmaceutical intermediate for the synthesis of various drugs. Its unique structure allows it to serve as a building block in the development of new medications with potential therapeutic benefits.
Used in the Synthesis of (Aminothiazolyl)acetanilide Derivatives:
In the field of diabetes treatment, (alphaR)-alpha-Hydroxy-N-[2-(4-nitrophenyl)ethyl]benzeneacetamide is used as an intermediate in the preparation of (aminothiazolyl)acetanilide derivatives. These derivatives are synthesized through coupling reactions and have shown promise in the treatment of diabetes, offering potential benefits to patients suffering from this chronic condition.

InChI:InChI=1S/C16H16N2O4/c19-15(13-4-2-1-3-5-13)16(20)17-11-10-12-6-8-14(9-7-12)18(21)22/h1-9,15,19H,10-11H2,(H,17,20)/t15-/m1/s1

Upstream product

• 611-71-2 (R)-Mandelic Acid 
• 29968-78-3 2-(4-nitrophenyl)ethylamine monohydrochloride 
• 24954-67-4 2-(p-nitrophenyl)ethylamine 
• 20698-91-3 (R)-methyl mandelate 
• 54256-33-6 (R)-(-)-5-phenyl-1,3-dioxolane-2,4-dione 
• 98-86-2 acetophenone 
• 611-73-4 Benzoylformic acid 
• 54385-47-6 (R)-Mandelsaeure, Natrium-Salz 

Downstream Products

• 521284-21-9 (R)-2-[[2′-(4-nitrophenyl)ethyl]amino]-1-phenylethanol hydrochloride 
• 391901-45-4 YM-208876 
• 223673-61-8 (R)-2-(2-aminothiazol-4-yl)-4'-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetanilide 
• 521284-22-0 (R)-2-[ [2-(4-aminophenyl)ethyl]-amino]-1-phenylethanol monohydrochloride 
• 223673-36-7 (R)-(4-aminophenylethyl)(2-hydroxy-2-phenylethyl)carbamic acid tert-butyl ester 
• 223673-35-6 ((2R)-2-hydroxy-2-phenylethyl)-[2-(4-nitrophenyl)ethyl]carbamic acid tert-butyl ester 
• 223673-34-5 (R)-2-(4-nitrophenylethylamino)-1-phenylethan-1-ol hydrochloride 

Relevant academic research and scientific papers

Concise Synthesis of Key Intermediate of Mirabegron via a Mixed Anhydride Method

An efficiently scalable synthesis of key intermediate toward mirabegron has been developed via a mixed anhydride method, employing PivCl instead of EDCI and HOBt. The developed process produced (R)-2-hydroxy-N-(4-nitrophenethyl)-2-phenylacetamide (10) in 91.5-92.3% yield and >99.0% HPLC purity under mild conditions. During this process, a side reaction induced by triethylamine hydrochloride was discovered and investigated, which was ultimately avoided by executing the reaction in a biphasic solvent system.

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.

Aryl or heteroaryl substituted pyrrolidine amide derivatives and application thereof

The invention discloses aryl or heteroaryl substituted pyrrolidine amide derivatives and an application thereof, in particular to a novel aryl or heteroaryl substituted pyrrolidine amide derivative and a pharmaceutical composition containing the same, which can be used for activating beta3-adrenergic receptor. The invention also relates to a method for preparing the compounds and pharmaceutical compositions, as well as an application thereof in preparing drugs for treating diseases or symptoms mediated by beta3-adrenergic receptor, and especially for treating the overactive bladder.

Amide substituted pyrrolidine amide derivatives and use thereof (by machine translation)

The invention discloses amide substituted pyrrolidine amide derivatives and their use, in particular, the invention relates to a novel class of amide substituted pyrrolidine amide derivatives containing such compounds and pharmaceutical composition, can be used to activate β 3 - adrenergic receptor. The invention also relates to processes for preparing such compounds and pharmaceutical compositions, and in the preparation of the treatment by the β 3 - adrenergic receptor activation mediated diseases or conditions, in particular the overactive bladder of the use of the medicament. (by machine translation)

Acyl-substituted pyrrolidine amide derivative and application thereof

The invention discloses an acyl-substituted pyrrolidine amide derivative and application thereof. Specifically, the invention relates to a novel acyl-substituted pyrrolidine amide derivative and a pharmaceutical composition containing the compound, which can be used for activation of beta3-adrenoceptor. The invention also relates to a method for preparing the compound and the pharmaceutical composition and their application in the preparation of beta3-adrenoceptor activation-mediated diseases or symptoms, especially overactive bladder.

Nitrogen heterocyclic ring group substituted amide derivative and application thereof

The invention discloses a nitrogen heterocyclic ring group substituted amide derivative and application thereof, particularly relates to a novel nitrogen heterocyclic ring group substituted amide derivative and a drug composition comprising the compound, and further relates to methods for preparing the compound and the drug composition, and application of the compound and the drug composition to preparation of drugs for treating diseases or symptoms, particularly overactive bladder, excited and mediated by beta 3-adrenergic receptors. The compound and the drug composition can be used for activating the beta 3-adrenergic receptors.

A METHOD FOR PREPARING MANDELIC ACID 4-NITROPHENYL ETHYLAMIDE FROM 4-NITROBENZYL CYANIDE

Preparation of a salt of 4-nitrophenyl ethylamine with (R)-mandelic acid and its use for the synthesis of mirabegron is disclosed. 4-Nitrophenyl ethylamine (1) is prepared by reduction of 4-nitrobenzyl cyanide (7) in a solvent with the use of a borane generated in-situ in the reaction mixture from NaBH4 and BF3.Et2O, 4-nitrophenyl ethylamine (1) being isolated from the solution as the mandelate 3.

A method for preparing milamila beilong

The invention discloses a method for preparing milamila beilong, relates to the technical field of pharmaceutical, comprising the following steps: R - mandelic acid and P ethylamine under high-temperature to amide condensation reaction, to obtain the intermediate (R)- 2 - hydroxy - N - (4 - nitrophenyl ethyl) - 2 - phenyl acetamide; then diisobutyl hydrogenated aluminum reducing amide carbonyl, to obtain the intermediate (R)- 2 - ((4 - nitrophenyl ethyl) amino) - 1 - phenyl ethanol hydrochloride; ammonium formate - Pd/C by nitro reduction system, to obtain the intermediate (R)- 2 - ((4 - amino ethyl) amino) - 1 - phenyl ethanol; finally with the amino thiazole acetic acid to generate a condensation reaction, to obtain milamila beilong. The invention prepared milamila beilong purity is good, high yield, synthetic line few steps, conditions is mild and controllable, the operation is simple, low cost, and is suitable for industrial production, and with extensive prospect and industrial application value.

Investigation of mechanistic pathway for trimethyl borate mediated amidation of (R)-mandelic acid for the synthesisof mirabegron, an antimuscarinic agent

The present work describes investigation of mechanistic pathway for trimethyl borate mediated amidation of (R)-mandelic acid (3) with 4-nitophenylethylamine (2) to provide (R)-2-hydroxy-N-[2-(4-nitrophenyl)ethyl]-2-phenylacetamide (4) during mirabegron synthesis. Plausible reaction mechanism is proposed by isolating and elucidating the active a-hydroxy ester intermediate 16 from the reaction mass. Trimethyl borate mediated approach proved to be selective in providing 4 without disturbing a-hydroxyl group and stereochemistry of the chiral center, and is also a greener, more economic and production friendly over the reported methods. The developed approach is rapid and efficient for the preparation of 4 with an overall yield of 85-87% and around 99.0% purity by HPLC at scale.

Synthesis of mirabegron intermediate (R)-2-hydroxy-N-(4-nitrophenyl ethyl)-2-phenylacetamide

The invention discloses synthesis of mirabegron intermediate (R)-2-hydroxy-N-(4-nitrophenyl ethyl)-2-phenylacetamide. The synthesis method comprises the following steps: performing esterification reaction on R-mandelic acid and triphosgene in a solvent under the existence of alkali to generate a lactide intermediate I; and performing acylation reaction on the intermediate I and 4-nitrophenylethylamine in a solvent to obtain a target product. The synthesis method avoids use of EDCI and HOBt with high price, has the advantages of easily available raw materials, low cost, simplicity in operationand few impurities, and is suitable for industrialized production.