140235-25-2

Usage

Chemical Properties

White Solid

InChI:InChI=1/C14H21NO3/c1-17-12-5-3-4-11(14(12)18-2)13(16)10-6-8-15-9-7-10/h3-5,10,13,15-16H,6-9H2,1-2H3

Upstream product

• 243640-27-9 4-[1-hydroxy-1-(2,3-dimethoxyphenyl)methyl]pyridine 
• 243640-28-0 4-(2,3-dimethoxybenzoyl)pyridine 
• 139290-70-3 tert-butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate 
• 498-94-2 isonipecotic acid 
• 84358-13-4 N-[(tert-butoxy)carbonyl]piperidine-4-carboxylic acid 
• 280115-99-3 tert-butyl 4-(chlorocarbonyl)-piperidine-1-carboxylate 
• 243640-26-8 tert-butyl 4-((2,3-dimethoxyphenyl)(hydroxy)methyl)piperidine-1-carboxylate 
• 139290-71-4 4-(2,3-Dimethoxybenzoyl)-1-piperidinecarboxylic acid 1,1-dimethylethyl ester 
• 139290-72-5 (2,3-dimethoxyphenyl)(piperidin-4-yl)methanone 

Downstream Products

• 243640-19-9 (2,3‐dimethoxyphenyl)(piperidine‐4‐yl)methanol 
• 311348-76-2 (S)-(-)-α-(2,3-dimethoxyphenyl)-4-piperidinemethanol 
• 243640-37-1 4-[1-hydroxy-1-(2,3-dimethoxyphenyl)methyl]-N-2-(4-fluorophen-1-oxo-ethyl)piperidine 
• 139290-69-0 (2,3-dimethoxy-phenyl)-{1-[2-(4-fluoro-phenyl)-ethyl]-piperidin-4-yl}-methanol 
• 869749-09-7 (R)-α-(2,3-dimethoxyphenyl)-4-piperidinemethanol, (2R,3R)-(-)-di-(p-toluoyl)tartaric acid salt 
• 1186018-69-8 [⁽¹⁸⁾F]MDL 100907 
• 1160298-48-5 (2,3-dimethoxyphenyl)-(1-(2-p-tolylethyl)-piperidin-4-yl)-methanol 
• 126405-25-2 (2,3-dimethoxyphenyl)-(1-(2-p-methoxyphenylethyl)-piperidin-4-yl)-methanol 
• 1160298-47-4 (2,3-dimethoxyphenyl)-(1-(2-p-nitrophenylethyl)-piperidin-4-yl)-methanol 
• 1160298-46-3 (2,3-dimethoxyphenyl)-(1-(p-fluorobenzyl)-piperidin-4-yl)-methanol 
• 869749-10-0 (R)-α-(2,3-dimethoxyphenyl)-4-piperidinemethanol, (2R,3R)-(-)-di-(p-anisoyl)tartaric acid salt 
• 175673-57-1 (-)-MDL 100907 
• 139290-65-6 R-(+)-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol 

Relevant academic research and scientific papers

Synthesis of 11C-labelled amides by palladium-mediated carboxamination using [11C]carbon monoxide, in situ activated amines and 1,2,2,6,6-pentamethylpiperidine

Twenty-seven 11C-labelled amides were synthesised using [11C]carbon monoxide in low concentrations, palladium(0), organohalides and amines in a small micro-autoclave (200 μL). The focus of the study was to improve the radiochemical yields in this palladium-mediated amide synthesis when employing less-reactive amines, such as methylamine, [(2R)-1-ethylpyrrolidin-2-yl]methylamine (40) and 2-(pyridin-2-yl)ethanamine (41). The radiochemical yields were improved when utilizing 1,2,2,6,6-pentamethylpiperidine (pempidine) in combination with the amine substrates. The 11C-labelled amides were obtained mostly in high radiochemical yields (in the range 16-94%) and the specific radioactivity varied between 650 and 1250GBq/μmol. 1-(1,3-Benzodioxol-5-yl[13C]carbonyl)piperidine (6a) was synthesised to verify the labelling position (δ = 169.8 ppm) using 13C NMR spectroscopy. The radiochemical purity of the target compounds was determined by analytical HPLC and exceeded 95%. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.

Highly enantioselective hydrogenation and transfer hydrogenation of cycloalkyl and heterocyclic ketones catalysed by an iridium complex of a tridentate phosphine-diamine ligand

Ir complexes of chiral phosphine-diamine ligands catalyse the hydrogenation and transfer hydrogenation of aryl-piperidin-4-yl methanones, and ketones bearing both an aryl group and secondary alkyl substituent with up to 98% e.e., and with substrate to catalyst ratios of up to 4000.

Synthesis and in vitro affinities of various MDL 100907 derivatives as potential 18F-radioligands for 5-HT2A receptor imaging with PET

Radiolabelled piperidine derivatives such as [11C]MDL 100907 and [18F]altanserin have played an important role in diagnosing malfunction in the serotonergic neurotransmission. A variety of novel piperidine MDL 100907 derivatives, possible to label with 18F-fluorine, were synthesized to improve molecular imaging properties of [11C]MDL 100907. Their in vitro affinities to a broad spectrum of neuroreceptors and their lipophilicities were determined and compared to the clinically used reference compounds MDL 100907 and altanserin. The novel compounds MA-1 (53) and (R)-MH.MZ (56) show Ki-values in the nanomolar range towards the 5-HT2A receptor and insignificant binding to other 5-HT receptor subtypes or receptors. Interestingly, compounds MA-1 (53), MH.MZ (55) and (R)-MH.MZ (56) provide a receptor selectivity profile similar to MDL 100907. These compounds could possibly be preferable antagonistic 18F-tracers for visualization of the 5-HT2A receptor status. Medium affine compounds (VK-1 (32), (51), (52), (54)) were synthesized and have Ki values between 30 and 120 nM. All promising compounds show log P values between 2 and 3, that is, within the range of those for the established radiotracers altanserin and MDL 100907. The novel compounds MA-1 (53) and (R)-MH.MZ (56) thus appear to be promising high affine and selective tracers of 18F-labelled analogues for 5-HT2A imaging with PET.

Synthesis, radiofluorination and first evaluation of (±)-[ 18F]MDL 100907 as serotonin 5-HT2A receptor antagonist for PET

In some psychiatric disorders 5-HT2A receptors play an important role. In order to investigate those in vivo there is an increasing interest in obtaining a metabolically stable, subtype selective and high affinity radioligand for receptor binding studies using positron emission tomography (PET). Combining the excellent in vivo properties of [11C]MDL 100907 for PET imaging of 5-HT2A receptors and the more suitable half-life of fluorine-18, MDL 100907 was radiofluorinated in four steps using 1-(2-bromoethyl)-4-[18F]fluorobenzene as a secondary labelling precursor. The complex reaction required an overall reaction time of 140 min and (±)-[18F]MDL 100907 was obtained with a specific activity of at least 30 GBq/μmol (EOS) and an overall radiochemical yield of 1-2%. In order to verify its binding to 5-HT2A receptors, in vitro rat brain autoradiography was conducted showing the typical distribution of 5-HT 2A receptors and a very low non-specific binding of about 6% in frontal cortex, using ketanserin or spiperone for blocking. Thus, [18F]MDL 100907 appears to be a promising new 5-HT2A PET ligand. Copyright

Processes for the preparation of (R)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol"

The present invention provides various processes for the preparation of (R)-±-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol. These processes may be characterized by the following scheme:

Use of MDL-100,907 for treatment of allergic and eosinophil mediated diseases

Methods of modulating eosinophil migration, chemotaxis or generation, in vitro, ex vivo, and in vivo are provided. Methods include contacting eosinophils with an amount of 5-HT2A receptor agonist or antagonist sufficient to modulate eosinophil migration, chemotaxis or generation.

Novel processes for the preparation of (R)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol

The present invention provides various processes for the preparation of (R)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol. These processes may be characterized by the following scheme:

Novel processes for the preparation or (R)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol

The present invention provides various processes for the preparation of (R)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol. These processes may be characterized by the following scheme:

A practical synthesis of the serotonin 5-HT(2a) receptor antagonist MDL 100907, its enantiomer and their 3-phenolic derivatives as precursors for [11C ]labeled PET ligands

A practical synthesis of the 3-phenolic precursor of MDL 100907, a selective 5-HT(2A) receptor antagonist, is described. The route was also applied to the enantiomeric series, thus affording the direct precursors of both 3-[11C]MDL 100907 and its enantiomer as ligands for positron emission tomography. Similar methodology was developed for the direct synthesis of MDL 100907 and its enantiomer, MDL 100009. The routes utilized classical optical resolution of the N-nor intermediates in at least 98% enantiomeric excess and easily afforded multigram amounts of the chiral precursors of a variety of N- and 3-O-substituted enantiomers. Copyright (C) 2000 Elsevier Science Ltd.