4746-63-8

Basic information

• Product Name: 2-HYDROXY-2,2-BIS(2-THIENYL) ACETIC ACID
• Synonyms: 2-HYDROXY-2,2-BIS(2-THIENYL) ACETIC ACID;Di-2-thienylglycolic Acid;2-HYDROXY-2,2-DITHIOPHEN-2-YLACETICACID;Aclidinium Impurity 3
• CAS NO: 4746-63-8
• Molecular Formula: C₁₀H₈O₃S₂
• Molecular Weight: 240.3
• Product Categories: Sulphur Derivatives;Heterocycles, Pharmaceuticals, Intermediates & Fine Chemicals
• Mol File: 4746-63-8.mol
• Article Data: 5

Chemical Properties

• Melting Point: 93 °C
• Boiling Point: 436.463°C at 760 mmHg
• Flash Point: 217.765°C
• Appearance: /
• Density: 1.528g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.683
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• Solubility: DMSO (Sparingly), Methanol (Slightly, Sonicated)
• PKA: 2.79±0.25(Predicted)
• Stability: Light Sensitive
• CAS DataBase Reference: 2-HYDROXY-2,2-BIS(2-THIENYL) ACETIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: 2-HYDROXY-2,2-BIS(2-THIENYL) ACETIC ACID(4746-63-8)
• EPA Substance Registry System: 2-HYDROXY-2,2-BIS(2-THIENYL) ACETIC ACID(4746-63-8)

Safety Data

• Hazardous Substances Data: 4746-63-8(Hazardous Substances Data)

Usage

Description

2-HYDROXY-2,2-BIS(2-THIENYL) ACETIC ACID, also known as Di-2-thienylglycolic Acid, is an organic compound with the molecular formula C10H8O3S2. It is an analog of Methyl Di(2-thienylglycolate) (M303765) and plays a crucial role in the pharmaceutical industry due to its involvement in the production of Tiotropium Bromide (T444850), a long-acting bronchodilator.

Uses

Used in Pharmaceutical Industry:
2-HYDROXY-2,2-BIS(2-THIENYL) ACETIC ACID is used as an intermediate compound for the production of Tiotropium Bromide (T444850), a long-acting bronchodilator. It is essential in the synthesis process, contributing to the development of medications that help in managing respiratory conditions such as chronic obstructive pulmonary disease (COPD) and asthma. 2-HYDROXY-2,2-BIS(2-THIENYL) ACETIC ACID's unique structure allows it to be a vital component in the creation of effective bronchodilator drugs, improving the quality of life for patients suffering from respiratory ailments.

InChI:InChI=1/C10H8O3S2/c11-9(12)10(13,7-3-1-5-14-7)8-4-2-6-15-8/h1-6,13H,(H,11,12)

Upstream product

• 4075-59-6 2-thiopheneglyoxylic acid 
• 5713-61-1 thiophen-2-yl magnesium bromide 
• 7333-07-5 2,2'-thenil 
• 28569-88-2 Ethyl (2,2'-Dithienyl)glycolate 
• 4075-58-5 thienylglycoxylate dethyle 
• 320345-99-1 aclidinium bromide 
• 7333-08-6 3,3'-Thenil 
• 211796-84-8 1,1-di(2'-thienyl)prop-2-yn-1-ol 
• 704-38-1 di(thiophen-2-yl)methanone 

Downstream Products

• 4408-82-6 2,2-di(thiophen-2-yl)acetic acid 
• 78196-89-1 (5-Phenyl-2-thienyl)(2-thienyl)acetic acid 
• 320345-99-1 aclidinium bromide 
• 320347-97-5 hydroxydithien-2-ylacetic acid 1-aza-bicyclo[2.2.2]oct-3(R)-yl ester 

Relevant articles and documents

Aclidinium bromide, a new, long-acting, inhaled muscarinic antagonist: In vitro plasma inactivation and pharmacological activity of its main metabolites

Aclidinium bromide is a novel, long-acting inhaled muscarinic antagonist drug in Phase III clinical trials for chronic obstructive pulmonary disease (COPD). The aims of this study were to evaluate the in vitro stability of the ester drug aclidinium in plasma from various species, and the in vitro and in vivo pharmacological activity of its hydrolysis metabolites. Following incubation of aclidinium in pooled samples of human, rat, guinea pig or dog plasma, the rate of hydrolysis was quantified by reversed phase ultra performance liquid chromatography and mass spectrometry. Tiotropium and ipratropium were used as comparators. The in vitro biochemical profile of the hydrolysis metabolites of aclidinium was assessed in human M1 to M5 muscarinic receptors and in a standard selectivity panel (85 G protein-coupled receptors [GPCRs], ion channels and enzymes). The bronchodilator activity of the metabolites of aclidinium bromide was studied in guinea pigs after acetylcholine-induced bronchoconstriction. Aclidinium was rapidly hydrolysed into carboxylic acid and alcohol derivatives in guinea pig, rat, human and dog plasma with half-lives of 38, 11.7, 2.4 and 1.8 min, respectively. In contrast, ≥70% of tiotropium and ipratropium remained unchanged in the plasma after 60 min of incubation. The carboxylic acid and alcohol metabolites had no significant affinity for any of the muscarinic receptors, other GPCRs, ion channels or enzymes studied and showed no relevant antibronchoconstrictory activity in vivo. These results suggest that aclidinium may have a reduced systemic exposure and therefore less propensity for class-related systemic side effects in the clinical setting.

Preparation method of tiotropium bromide intermediate

The invention belongs to the technical field of drug synthesis, and provides a preparation method of a tiotropium bromide important intermediate bis (2-dithienyl) glycolic acid ester, which comprises the following steps: reacting bis (2-thiophene) ketone as a starting material with sodium ethynyl under the catalysis of indium bromide to obtain 1, 1-bis (2-thienyl) propyl-2-alkyn-1-ol, oxidizing by acidic potassium permanganate to generate di (2-dithienyl) glycolic acid, and finally, carrying out esterification on the di (2-dithienyl) glycolic acid and methyl iodide to obtain di (2-dithienyl) methyl glycolate. Reaction conditions are milder, starting materials are cheap and easy to obtain, generation of heterogeneous impurities can be avoided, the product quality is more stable, and the method is suitable for industrial production.

A Study of Some Thiophene Analogues of Glycolic Acid

Reaction of phenyl(3-thienyl)glycolic acid (1) with AlCl3 in benzene solution leads to the formation of 4H-indenothiophene-4-carboxylic acid (2) whereas analogous reaction of phenyl(2-thienyl)glycolic acid (4) produces no indenothiophene but only a mixture of 5 and 6.In the case of di-(2-thienyl)glycolic acid (14b) and di-(3-thienyl)glycolic acid (16b) analogous results are obtained, with the former leading to the formation of 15 and the latter producing 17.In the case of the (benzothienyl)phenylglycolic analogues of 1 and 4 the acids were unstable to heat so that the esters, ethyl (2-benzothienyl)phenylglycolate (21) and ethyl (3-benzothienyl)phenylglycolate (20), upon treatment with AlCl3 in benzene led to cyclized products only.The former gave 23 which was saponified and decarboxylated to yield 25 and compared with an authentic sample obtained by synthesis.Ester 20 similarly gave 22 which was similarly converted to the known 24.A mechanistic explanation of these findings is proposed.