376592-93-7

Basic information

• Product Name: 3''-AMINO-2''-HYDROXY-BIPHENYL-3-CARBOXYLIC ACID
• Synonyms: 3''-AMINO-2''-HYDROXY-BIPHENYL-3-CARBOXYLIC ACID;3'-Amino-2'-hydroxy-[1,1'-biphenyl]-3-carboxylic acid;Eltrombopag Intermediate 2;EltroMbopag I;3-(3-aMino-2-hydroxyphenyl)benzoic acid;[1,1'-Biphenyl]-3-carboxylic acid, 3'-aMino-2'-hydroxy-;3''-AMINO-2''-HYDROXY-BIPHENYL-3-CARBOXYLIC;Eltrombopag olamine Intermediate 1
• CAS NO: 376592-93-7
• Molecular Formula: C₁₃H₁₁NO₃
• Molecular Weight: 229.234
• EINECS: 1592732-453-0
• Mol File: 376592-93-7.mol

Chemical Properties

• Melting Point: 222 °C(dec.)
• Boiling Point: 474.8±45.0 °C(Predicted)
• Appearance: /
• Density: 1.364
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• Solubility: DMSO (Slightly), Methanol (Slightly, Heated)
• PKA: 3.99±0.10(Predicted)
• CAS DataBase Reference: 3''-AMINO-2''-HYDROXY-BIPHENYL-3-CARBOXYLIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: 3''-AMINO-2''-HYDROXY-BIPHENYL-3-CARBOXYLIC ACID(376592-93-7)
• EPA Substance Registry System: 3''-AMINO-2''-HYDROXY-BIPHENYL-3-CARBOXYLIC ACID(376592-93-7)

Safety Data

• Hazardous Substances Data: 376592-93-7(Hazardous Substances Data)

Upstream product

• 376591-95-6 2'-hydroxy-3'-nitro-biphenyl-3-carboxylic acid 
• 695-96-5 2-bromo-4-chlorophenol 
• 25487-66-5 3-Carboxyphenylboronic acid 
• 376592-57-3 5'-chloro-2'-hydroxybiphenyl-3-carboxylic acid 
• 376592-58-4 5'-chloro-2'-hydroxy-3'-nitrobiphenyl-3-carboxylic acid 
• 89-64-5 p-chloro-o-nitrophenol 
• 15969-10-5 2-bromo-4-chloro-6-nitro-phenol 
• 688363-79-3 1-bromo-3-nitro-2-[(phenylmethyl)oxy]benzene 
• 13073-25-1 2-bromo-6-nitro-phenol 
• 28165-50-6 2-amino-6-bromophenol 
• 186663-74-1 tert-butyl (2-hydroxyphenyl)carbamate 
• 618-51-9 3-Iodobenzoic acid 
• 88-75-5 2-hydroxynitrobenzene 
• 585-76-2 m-bromobenzoic acid 

Downstream Products

• 376591-99-0 3’-{N’-[1-(3,4-dimethylphenyl)-3-methyl-5-oxo-1,5-di-hydropyrazol-4-ylidene]hydrazino}-2’-hydroxybiphenyl-3-carboxylic acid 
• 893736-72-6 2′-hydroxy[1,1-biphenyl]-3-carboxylic acid 

Relevant articles and documents

PROCESS FOR THE PREPARATION OF KEY INTERMEDIATES FOR THE SYNTHESIS OF ELTROMBOPAG OR SALT THEREOF

Object of the present invention is an improved process for the preparation of key intermediates for the synthesis of Eltrombopag, passing through/using intermediate 5'-Chloro-2'-hydroxy[1,1'-biphenyl]-3-carboxylic acid alkaline metal salt of formula: wherein A is an alkaline metal.

An improved process for the preparation of Eltrombopag Olamine and its intermediates

The present invention relates to an improved process for the purification of Eltrombopag olamine of compound of formula (2). The present invention also relates to an improved process for the preparation of Eltrombopag olamine intermediates and further conversion to Eltrombopag olamine of a compound of formula (2).

Preparation method of drug intermediate for treating idiopathic blood diseases

The invention provides a preparation method of a drug intermediate for treating idiopathic blood diseases, which comprises the following steps: by using 2'-hydroxy-3'-nitrobiphenyl-3-carboxylic acid as a starting material and adopting a hydrazine hydrate-iron-carrier reduction method, avoiding the conventional Pd/C hydrogenation reduction reaction conditions, and carrying out aftertreatment by regulating the pH value and filtering, and the operability of amplify production is strong. Compared with Pd/C, the price advantage of hydrazine hydrate is obvious, the material cost can be greatly reduced, and the method is very suitable for industrial production.

Preparation method of eltrombopag intermediate and preparation method of eltrombopag diethanolamine salt

The invention provides a preparation method of an eltrombopag intermediate and a preparation method of eltrombopag diethanolamine salt, and relates to the technical field of medicinal chemistry. According to the preparation method of the eltrombopag intermediate, p-bromophenol is taken as a raw material, and the problem of poor selectivity of nitration reaction is solved. After iodination, the coupling reaction yield of the intermediate compound as shown in a formula (I) and phenylboronic acid is high. Subsequently reduction reaction is carried out, the debromination reaction is complete, the yield is 90% or more, the refining is simpler, and the synthesis yield of the compound of the formula (I) is higher and the operation is simple. Through the improvement, the yield of the key compound shown as the formula (I) is relatively high, the subsequent treatment operation is simple, the process is easy for amplified production, the yield of the whole synthesis process of the eltrombopag diethanolamine salt is 48.1%, the operation is simple, less three wastes are generated, and the synthesis process is suitable for amplified production.

Synthetic method of eltrombopag intermediate and synthetic method of eltrombopag

The invention relates to the field of medicine synthesis, in particular to a synthesis method of an eltrombopag intermediate and a synthesis method of eltrombopag. The synthesis method of the eltrombopag intermediate comprises the following steps: mixing 2'-hydroxyl-3'-nitrobiphenyl-3-carboxylic acid or 5'-chloro-2'-hydroxyl-3'-nitrobiphenyl-3-carboxylic acid with an alkali, a catalyst and water,introducing hydrogen, and carrying out a hydrogenation reaction to form the eltrombopag intermediate. The synthesis steps are simplified, the generation of impurities is reduced, and the yield and purity are improved.

Synthetic method of eltrombopag intermediate

The application discloses a synthetic method of an eltrombopag intermediate, comprising: subjecting 2-aminophenol derivative shown as formula (II) as a raw material to react with an aromatic reagent shown as formula (III) to obtain an intermediate product shown as formula (IV); using the intermediate product shown as formula (IV) as a raw material to prepare the eltrombopag intermediate shown as formula (I), wherein R1 is selected from amino derivatives, and R2 is selected from halogen and sulfonyloxy group. The synthetic method has few reaction steps; the starting material is simple; the synthetic method is simpler, more economical and greener.

A [...] intermediate 2 - hydroxy -3 - (between carboxyl phenyl) aniline preparation method (by machine translation)

The invention provides a [...] intermediate 2 - hydroxy - 3 - (between carboxyl phenyl) aniline of the preparation method. The use of 2 - amino - 4 - chlorophenol as raw materials, in order to urea protection, after brominated, benzylating, Suzuki coupling reaction, the water releasing urea protection, hydrogenated dechlorination and benzyl, to obtain the 2 - hydroxy - 3 - (between carboxyl phenyl) aniline. The method compared with the traditional method, with simple operation, mild condition easy controlled, safety and environmental protection, advantage of high productive rate, is suitable for industrial mass production. (by machine translation)

Preparation method of eltrombopag

The invention relates to the technical field of medicine manufacturing, and discloses a preparation method of eltrombopag. The preparation method comprises the following steps: 1, sequentially carrying out a continuous reaction on a starting material I, glacial acetic acid and hydrobromic acid until the reaction is completed to obtain an intermediate I; 2, reducing the intermediate I by hydrazinehydrate under catalytic action of palladium to obtain an intermediate II; and 3, carrying out diazotization addition on the intermediate II to obtain the eltrombopag. According to the method, nitryl is prevented from being directly reduced by hydrogen on the premise that the medicine quality is guaranteed, so that production can be safely amplified, and market competitiveness of the variety is improved.

Preparation method of eltrombopag medicine for treating idiopathic thrombocytopenic purpura

The invention discloses a preparation method of an eltrombopag medicine for treating idiopathic thrombocytopenic purpura. A chemical name of the eltrombopag is 3-{(2Z)-2-[1-(3,4-xylyl)-3-methyl-5-oxo-1,5-dihydrogen-4H-pyrazole-4-idene]hydrazine}-2- hydroxyl-3-biphenyl carboxylic acid-2-amine ethanol salt. The preparation method has the advantages that the preparation process is concise, the raw materials are easy to obtain, the hypertoxic iodomethane is not used, the economic and environment-friendly effects are realized, the industrialization is favorably realized, the economic and technicaldevelopment of the crude drug of the eltrombopag can be promoted, the production cost is reduced, and the preparation method is suitable for large-batch production.

Novel method for preparing Eltrombopag intermediate

The invention provides a method for preparing a compound shown as the formula I (please see the formula in the description). The method specifically comprises the following steps that 1, a compound shown as the formula (II) (please see the formula in the description) reacts with a compound shown as formula (V) (please see the formula in the description) under the alkaline condition to generate a compound shown as the formula (III) (please see the formula in the description); 2, the compound shown as the formula (III) (please see the formula in the description) reacts with a compound shown as the formula (VI) (please see the formula in the description) under the alkaline condition in the presence of palladium carbon to generate a compound shown as the formula (IV) (please see the formula in the description); 3, the compound shown as the formula (IV) (please see the formula in the description) reacts in the presence of palladium carbon and a hydrogen source under the alkaline condition to generate the compound shown as the formula (I) (please see the formula in the description). According to the method, design is ingenious, protecting group removal, dechlorination and nitro reduction are together completed in the final hydrogenation process, and the purity of the obtained compound shown as the formula (I) (please see the formula in the description) is high; the most important thing is that compared with other Suzuki coupling agents, cost of palladium carbon is lower, a source of palladium carbon is wide and easy to obtain, palladium carbon can be directly recycled and reused after being simply filtered and separated, and therefore the material cost is greatly reduced; meanwhile, emission of three wastes is reduced, and the method is quite suitable for industrialized production.