209747-05-7

Basic information

• Product Name: Tolterodin hydrogen tartrate
• Synonyms: Tolterodin hydrogen tartrate;Tolterodin tartrate;(R)-Tolterodine L-tartrate
• CAS NO: 209747-05-7
• Molecular Formula: C26H37NO7
• Molecular Weight: 475.57448
• Mol File: 209747-05-7.mol

Chemical Properties

• Boiling Point: 442.2 °C at 760 mmHg
• Flash Point: 192.1 °C
• Appearance: /
• CAS DataBase Reference: Tolterodin hydrogen tartrate(CAS DataBase Reference)
• NIST Chemistry Reference: Tolterodin hydrogen tartrate(209747-05-7)
• EPA Substance Registry System: Tolterodin hydrogen tartrate(209747-05-7)

Safety Data

• Hazardous Substances Data: 209747-05-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Tolterodine hydrogen tartrate is utilized as a therapeutic agent for the management of overactive bladder. It is employed to alleviate symptoms such as urinary frequency and incontinence by targeting and blocking the nerve signals that cause these conditions. This results in a more controlled and comfortable urinary experience for patients suffering from overactive bladder.
Common side effects associated with the use of tolterodine hydrogen tartrate include dry mouth, constipation, and headache. It is crucial for patients to adhere to the dosage and usage instructions provided by their healthcare professionals to ensure a safe and effective treatment regimen.

Upstream product

• 87-69-4 L-Tartaric acid 
• 124936-74-9 N,N-diiso-propyl-3-(2-hydroxy-5-methylphenyl)-3-phenylpropanamine 
• 837376-36-0 3-(2-hydroxy-5-methylphenyl)-N,N-diisopropyl-3-phenylpropan-1-aminium bromide 
• 124936-70-5 N,N-Diisopropyl-3-(2-hydroxyphenyl)-3-phenylpropylamine 
• 897314-72-6 (+/-)-N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenyl-propanamide 
• 1043911-42-7 N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenyl-propylamine L-tartrate 
• 4850-49-1 1-phenyl-1,3-propanediol 
• 851789-43-0 3-phenyl-3-(2'-hydroxy-5'-methyl)phenylpropanol-1 
• 94-02-0 ethyl 3-oxo-3-phenylpropionate 
• 92-48-8 6-methylcoumarin 
• 98-80-6 phenylboronic acid 
• 827007-19-2 (R)-6-methyl-4-phenyl-3,4-dihydrochromen-2-one 
• 828933-86-4 (4R)-6-methyl-4-phenylchroman-2-ol 
• 108-18-9 diisopropylamine 

Downstream Products

• 848768-06-9 (R)-3-[2-(benzyloxy)-5-methylphenyl]-N,N-diisopropyl-3-phenylpropan-1-amine 
• 380636-50-0 (R)-5-hydroxymethyl tolterodine fumarate salt 
• 207679-81-0 (R)-2-[3-(diisopropylamino)-1-phenylpropyl]-4-(hydroxymethyl)-phenol 
• 214601-54-4 (R)-[4-benzyloxy-3-(3-diisopropylamino-1-phenyl-propyl)-phenyl]-methanal 
• 156755-37-2 {4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]phenyl}methanol 

Relevant articles and documents

Computationally-Led Ligand Modification using Interplay between Theory and Experiments: Highly Active Chiral Rhodium Catalyst Controlled by Electronic Effects and CH–π Interactions

A chiral ligand for the rhodium-catalyzed asymmetric 1,4-addition of an arylboronic acid to a coumarin substrate that could markedly reduce catalyst loading was developed using interplay between theoretical and experimental approaches. Evaluation of the transition states for insertion and for hydrolysis of intermediate complexes (which were emphasized in response to the experimental results) using DFT calculations at the B97D/6-31G(d) level with the LANL2DZ basis set for rhodium revealed that: (i) the electron-poor nature of the ligands and (ii) CH–π interactions between the ligand and coumarin substrates played significant roles in both acceleration of insertion and inhibition of ArB(OH)2 decomposition (protodeboronation). The computationally-designed ligand, incorporating the above information, enabled a decrease in the catalyst loading to 0.025 mol% (S/C=4,000), which is less than one one-hundredth relative to past catalyst loadings of typically 3 mol%, with almost complete enantioselectivity. Furthermore, the gram-scale synthesis of the urological drug, (R)-tolterodine (l)-tartrate, was demonstrated without the need of intermediate purification. (Figure presented.).

Ligand-Phospholipid Conjugation: A Versatile Strategy for Developing Long-Acting Ligands That Bind to Membrane Proteins by Restricting the Subcellular Localization of the Ligand

We hypothesized that if drug localization can be restricted to a particular subcellular domain where their target proteins reside, the drugs could bind to their target proteins without being metabolized and/or excreted, which would significantly extend the half-life of the corresponding drug-target complex. Thus, we designed ligand-phospholipid conjugates in which the ligand is conjugated with a phospholipid through a polyethylene glycol linker to restrict the subcellular localization of the ligand in the vicinity of the lipid bilayer. Here, we present the design, synthesis, pharmacological activity, and binding mode analysis of ligand-phospholipid conjugates with muscarinic acetylcholine receptors as the target proteins. These results demonstrate that ligand-phospholipid conjugation can be a versatile strategy for developing long-acting ligands that bind to membrane proteins in drug discovery.

Process for the preparation of N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)- 3-phenyl propylamine and its salts starting from a novel intermediate

The invention concerns an improved process for the preparation of tolterodine (N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenyl propylamine) and its salts, in particular for the preparation of the tartrate salt, and more in particular for the (+)-(R) enantiomer of tolterodine L-tartrate, starting from a novel intermediate, N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenyl-2-propenamide which can be used as pure Z or E isomer or as a mixture of Z and E isomers.

PROCESS FOR THE PREPARATION OF N,N-DIISOPROPYL-3-(2-HYDROXY-5-METHYLPHENYL)- 3-PHENYL PROPYLAMINE AND ITS SALTS STARTING FROM A NOVEL INTERMEDIATE

The invention concerns an improved process for the preparation of tolterodine (N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenyl propyl amine) and its salts, in particular for the preparation of the tartrate salt, and more particularly for the (+)-(R) enantiomer of tolterodine L-tartrate, starting from a novel intermediate, N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3- phenyl-2-propenamide, which can be used as pure Z or E isomer or as a mixture of Z and E isomers. When the target is the preparation of the enantiomer (R)-(+)-(N,N- diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenylpropylamine) and diastereomeric crystallization of suitable compound is applied, the present invention covers also the use of racemisation of undesired (S)-(-)- (N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3 -phenyl propylamine) enantiomer and its recycle in the process.

Chiral separation of tolterodine tartrate using amylosed base immobilized stationary phase in LC method

High-performance liquid chromatographic method was developed and validated for chiral separation of tolterodine tartrate. It was achieved on Chiral pack IA (immobilized amylosed based polysaccharides stationary phase) using a mobile phase of hexane: 2-propanol: triethylamine: trifluroacetic acid (91:9:0.2:0.1 v/v) at a flow rate 1.1 mL/min. Resolution between S-tolterodine tartrate and R-tolterodine tartrate was found to be 2.9. Developed LC method was used for the quantification of S-tolterodine tartrate as chiral impurity in Rtolterodine tartrate. The developed method was extensively validated and proved to be robust. The calibration curve for S-tolterodine tartrate showed an excellent linearity over the concentrations range 0.1 to 10 μg/mL. The limit of detection and limit of quantification for S-tolterodine tartrate were 0.11 μg/mL and 0.34 μg/mL respectively. Average recovery of S-isomer was in the range of 97.30 to 101.59 %. S-tolterodine tartrate and R-tolterodine tartrate solutions in mobile phase were found to be stable for 48 h. The proposed method was short runtime, precise and accurate for quantitative determination of S-isomer in R-tolterodine tartrate in API and its solid oral dosage form.

PROCESS FOR THE PREPARATION OF (R)-2-(3-DIISOPROPYLAMINO)-1-PHENYLPROPYL)-4METHYLPHENOL AND SALTS THEREOF

The present invention relates to an improved process for the preparation of Tolterodine or salts thereof, which comprises the use of 3-(2-methoxy-5-methylphenyl)-3-phenylpropyl methane sulfonate.

PROCESS FOR PREPARING TOLTERODINE AND THE L-TARTRATE THEREOF

The present invention relates to a process for preparing tolterodine and the L-tartrate thereof. The preparation consists of the following steps: A) ammonolysis reaction between diisopropylamine and compound 2 (3,4-dihydro-6-methyl-4-phenyl-2H-benzopyran-

IMPROVED PROCESS FOR THE PREPARATION OF (R)-2-(3-DIISOPROPYLAMINO)-1-PHENYLPROPYL)-4METHYLPHENOL AND SALTS THEREOF

The present invention relates to an improved process for the preparation of Tolterodine or salts thereof, which comprises the use of 3-(2-methoxy-5-methylphenyl)-3-phenylpropyl methane sulfonate.

A PROCESS FOR THE PREPARATION OF TOLTERODINE TARTRATE

The present invention relates to provide a process for the preparation of (+)-(R)-Tolterodine-L-tartrate, comprises a step of aminating hydroxyl protected 3-(2-methoxy-5-methylphenyl)-3-phenyl propanol of formula (V) with diisopropylamine in the presence of water to obtain N, N-diisopropyl-3-(2-methoxy-5-methylphenyl)-3-phenylpropyl amine of formula (VI).

A PROCESS FOR THE PREPARATION OF TOLTERODINE TARTRATE

The present invention relates to provide an improved process for the preparation of tolterodine or salt thereof, comprises a step of reducing 3-(2-methoxy-5-methylphenyl) -3-phenyl propionic acid of formula (III) in the presence of a reducing agent, an acidic reagent and a solvent to obtain 3-(2-methoxy-5-methylphenyl) -3-phenyl propanol of formula (IV).