200801-70-3

Usage

InChI:InChI=1/C22H31NO2/c1-16(2)23(17(3)4)13-12-20(19-8-6-5-7-9-19)21-14-18(15-24)10-11-22(21)25/h5-11,14,16-17,20,24-25H,12-13,15H2,1-4H3

Upstream product

• 959624-24-9 (2-hydroxy-4-phenyl-3,4-dihydro-2H-chromen-6-yl)methanol 
• 108-18-9 diisopropylamine 
• 250214-39-2 (-)-N,N-diisopropyl-3-(2-benzyloxy-5-hydroxymethylphenyl)-3-phenylpropylamine 
• 214601-16-8 N,N-diisopropyl-3-(2-hydroxy-5-methyloxycarbonylphenyl)-3-phenylpropanamine 
• 2687-12-9 cinnamyl chloride 
• 87462-12-2 N,N-diisopropyl-3-phenyl-2-propen-1-amine 
• 21087-29-6 trans-3-phenylprop-2-enyl chloride 
• 173948-30-6 (E)-N,N-diisopropyl-3-phenylprop-2-en-1-amine 
• 99-76-3 methyl 4-hydroxylbenzoate 
• 380636-44-2 (4R,4S)-2-(R,S)-hydroxy-4-phenylchromane-6-carboxylic acid methyl ester 
• 250214-44-9 2-(3-(diisopropylamino)-1-phenylpropyl)-4-(hydroxyl-methyl)phenyl isobutyrate 
• 14371-10-9 (E)-3-phenylpropenal 
• 623-05-2 (4-hydroxyphenyl)methanol 
• 906532-26-1 3-(N,N-diisopropylamino)-1-phenylpropan-1-ol 

Downstream Products

• 207679-81-0 (R)-2-[3-(diisopropylamino)-1-phenylpropyl]-4-(hydroxymethyl)-phenol 
• 286930-02-7 fesoterodine 
• 156755-20-3 PNU 200577 l-mandelate salt 
• 286930-03-8 fesoterodine fumarate 
• 1350462-15-5 lithium (R)-(+)-2-(3-diisopropylamino-1-phenylpropyl)-4-hydroxymethylphenol 
• 286930-03-8 fesoterodine fumarate 
• 1333234-72-2 (R)-2-[3-(diisopropylamino)-1-phenylpropyl]-4-(hydroxymethyl)phenol (R)-2-acetoxy(phenyl)acetate 
• 260389-90-0 5-hydroxymethyl tolterodine 

Relevant academic research and scientific papers

Photochemistry of a novel antimuscarinic drug fesoterodine and identification of its photodegradation products by LC-ESI-MS studies

Fesoterodine (FESO) is a novel muscarinic receptor antagonist for the treatment of overactive bladder syndrome. The aim of this work was to study the photodegradation of FESO, to determine its kinetics and to identify the photodegradation products. The photochemistry of FESO was investigated in sample solutions exposed to a UV-A (320-400 nm) and UV-C irradiation (100-280 nm) at room temperature. The photodegradation process was monitored by means of liquid chromatography method equipped with monolithic column and photodiode array detector. This drug is more photolabile under UV-C light. In methanol-water solution (1:1, v/v), approximately 62.5% of FESO decomposes after 60 min of UV-C irradiation, whereas under 6 h of UV-A light only 4.9% decomposes. FESO was shown to be photolabile and its photodegradation reaction followed the zero-order kinetics with the rate constant k = 0.5503 min-1, and t1/2 and t90% obtained were 46.92 min and 9.38 min, respectively. The main degradation products were isolated by semi-preparative liquid chromatography and identified by liquid chromatography coupled to an electrospray ionization mass spectrometry. The powdered and intact tablets were also exposed to UV-C irradiation. Based on the obtained results, a complete drug photodegradation pathway was proposed.

Synthetic Method of Intermediate for Fesoterodine

The present invention relates to a method for producing 3-(3-diisopropylamino-1-phenylpropyl)-4-hydroxy benzenemethanol, which is an intermediate product useful for producing fesoterodine, by using ethyl benzoylacetate as a starting material. The producin

Formal synthesis of fesoterodine by acid-facilitated aromatic alkylation

The competitive muscarinic receptor antagonist fesoterodine is a congener of tolterodine and has better efficiency compared to tolterodine. In this study, we present an efficient synthesis of the fesoterodine intermediate 3-(3-diisopropylamino-1-phenylpropyl)-4-hydroxybenzaldehyde from ethyl benzoylacetate by Friedel-Crafts alkylation in the presence of an acid as a key reaction step. The synthesis is carried out by the reduction of the ketoester to a 1,3-diol, diisopropylamine substitution, and Friedel-Crafts alkylation, followed by reduction and chiral resolution.

PROCESS FOR THE PREPARATION OF 2-HYDROXY-4-PHENYL-3,4-DIHYDRO-2H-CHROMEN-6-YL-METHANOL AND (R)-FESO-DEACYL

The present invention regards an improved and industrially advantageous process for the preparation of the 2-hydroxy-4-phenyl-3,4-dihydro-2H-chromen-6-yl-methanol intermediates, also called “feso chromenyl” and (R)-2-[3-(diisopropylamino)-1-phenylpropyl]-4-(hydroxymethyl)phenol, also called “(R)-feso deacyl”, which are in turn used in the synthesis of fesoterodine and in particular of fesoterodine fumarate. This process utilises reagents which are non-toxic and manageable at industrial level and enables obtaining a new stable and non-hygroscopic crystalline form of the key intermediate “(R)-feso deacyl”, called form B.

The lactol route to fesoterodine: An amine-promoted Friedel-Crafts alkylation on commercial scale

We report the discovery and optimization of an amine-promoted Friedel-Crafts alkylation of cinnamaldehyde with 4-hydroxymethyl phenol. This reaction has been used successfully on commercial scale (200 kg) in the context of the manufacture of fesoterodine, a muscarinic antagonist used for the treatment of overactive bladder. Reductive aminations of diisopropylamine and lactol 4 are also discussed, as well as the resolution of the racemic amine rac-2 into its enantiomerically pure form.

PROCESS FOR THE PREPARATION OF 2 -HYDROXY- 4 -PHENYL -3, 4 -DIHYDRO-2H-CHROMEN- 6 -YL -METHANOL AND (R) - FESO - DEACYL

The present invention regards an improved and industrially advantageous process for the preparation of the 2-hyaroxy-4-phenyl-3,4-dihydro-2H-chromen-6-yl-methanol intermediates, also called "feso chromenyl" and (R)-2-[3-(diisopropylamino)-l- phenylpropyl]-4-(hydroxymethyl)phenol, also called "(R)-feso deacyl", which are in turn used in the synthesis of fesoterodine and in particular of fesoterodine furnarate. This process utilises reagents which are non-toxic and manageable at industrial level and enables obtaining a new stable and non-hygroscopic crystalline form of the key intermediate "(R)-feso deacyl", called form B.

PREPARATION PROCESS OF FESOTERODINE AND INTERMEDIATES

The present invention relates to a process of synthesis of 3,3 dipheylpropylamines, which may be used as pharmaceutical intermediates in the preparation of their pharmacologically active derivatives such as fesoterodine, tolterodine, their enantiomers, pharmaceutically acceptable salts and related compounds useful as antimuscarinic agents.

Process for preparation of 3-(2-hydroxy-5-substituted phenyl)-3-phenylpropylamines, intermediates for making hydroxytolterodine

A process is described for the preparation of 3-(5-formyl-2-hydroxyphenyl)-3-phenylpropylamine derivatives, intermediates which can be used for preparation of agents for urinary incontinence therapy, specifically to 2-(3-(diisopropylamino)-1-phenylpropyl)-4-(hydroxymethyl)phenol and its prodrugs.

SHORT SYNTHESIS OF TOLTERODINE, INTERMEDIATES AND METABOLITES

A process is described for the preparation of intermediates which can be used for preparation of agents for urinary incontinence therapy, specifically to 2-(3-(diisopropylamino)- 1-phenylpropyl)-4-(hydroxymethyl)phenol and its prodrugs.

Fesoterodine Substantially Free of Dehydroxy Impurity

Provided herein is an impurity of fesoterodine, fesoterodine dehydroxy impurity, 2-[(1R)-3-[bis(1-methylethy)amino]-1-phenylpropyl]-4-methylphenyl isobutyrate, and a process for preparing and isolating thereof. Provided further herein is a highly pure fesoterodine or a pharmaceutically acceptable salt thereof substantially free of fesoterodine dehydroxy impurity, process for the preparation thereof, and pharmaceutical compositions comprising highly pure fesoterodine or a pharmaceutically acceptable salt thereof substantially free of dehydroxy impurity. Provided also herein is a pharmaceutical composition comprising solid particles of pure fesoterodine fumarate substantially free of dehydroxy impurity, wherein 90 volume-percent of the particles (D90) have a size of less than about 200 microns.