130342-81-3

Basic information

• Product Name: RTI-COC 32
• Synonyms: RTI-COC 32;(1R,2S,3S,5S)-3-(4-Methylphenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid methyl ester;(1β,5β)-3β-(4-Methylphenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2β-carboxylic acid methyl ester;RTI-32
• CAS NO: 130342-81-3
• Molecular Formula: C₁₇H₂₃NO₂
• Molecular Weight: 273.37
• Mol File: 130342-81-3.mol

Chemical Properties

• Boiling Point: 368.7°Cat760mmHg
• Flash Point: 124.3°C
• Appearance: /
• Density: 1.084g/cm³
• Vapor Pressure: 1.25E-05mmHg at 25°C
• Refractive Index: 1.537
• PKA: 10.01±0.60(Predicted)
• CAS DataBase Reference: RTI-COC 32(CAS DataBase Reference)
• NIST Chemistry Reference: RTI-COC 32(130342-81-3)
• EPA Substance Registry System: RTI-COC 32(130342-81-3)

Safety Data

• Hazardous Substances Data: 130342-81-3(Hazardous Substances Data)

Usage

InChI:InChI=1/C17H23NO2/c1-11-4-6-12(7-5-11)14-10-13-8-9-15(18(13)2)16(14)17(19)20-3/h4-7,13-16H,8-10H2,1-3H3/t13-,14+,15+,16-/m0/s1

Upstream product

• 50373-10-9 (R)-(-)-anhydroecgonine methyl ester 
• 4294-57-9 para-methylphenylmagnesium bromide 
• 50373-10-9 methyl ecgonidine 
• 481-37-8 ecgonine 
• 53-21-4 (-)-cocaine hydrochloride 
• 2417-95-0 p-tolyllithium 
• 50-36-2 Cocaine 

Downstream Products

• 204009-33-6 2β-carbomethoxy-3β-(3'-iodo-4'-methylphenyl)tropane 
• 409360-20-9 2β-p-tolylcarbonyl-3β-p-tolyltropane 
• 204071-17-0 (1R,2S,3S,5S)-8-Methyl-3-p-tolyl-8-aza-bicyclo[3.2.1]octane-2-carbonyl chloride 
• 398497-73-9 (1R,2S,3S,5S)-8-Methyl-3-p-tolyl-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid 3-methanesulfonyloxy-propyl ester 
• 204009-17-6 2β-carbomethoxy-3β-(4'-methyl-3'-iodophenyl)nortropane 
• 1061288-50-3 3β-(4-methylphenyl)-2β-[3'-(4-fluorobenzyl)isoxazol-5-yl]tropane 
• 1061288-69-4 3β-(4-methylphenyl)-2β-[3'-methyl-4'-(4-fluorophenyl)isoxazol-5-yl]tropane 
• 1061288-64-9 3β-(4-methylphenyl)-2β-[3'-(4-methoxybenzyl)isoxazol-5-yl]tropane 
• 1061288-84-3 3β-(4-methylphenyl)-2β-[3'-methyl-4'-(4-methoxyphenyl)isoxazol-5-yl]tropane 
• 1061288-55-8 3β-(4-methylphenyl)-2β-[3'-(4-chlorobenzyl)isoxazol-5-yl]tropane 

Relevant articles and documents

68Ga-Labelled Tropane Analogues for the Visualization of the Dopaminergic System

The development of radiometal-labelled pharmaceuticals for neuroimaging could offer great potential due to easier handling during labelling and availability through radionuclide generator systems. Nonetheless, to date, no such tracers are available for positron emission tomography, primarily owing to the challenge of crossing the blood–brain barrier (BBB) and loss of affinity through chelator attachment. We have prepared a variety of 68Ga-labelled phenyltropanes showing that, through a simple hydrocarbon-linker, it is possible to introduce a chelator onto the lead structure while maintaining its high affinity for hDAT (human dopamine transporter) and simultaneously achieving adequate lipophilicity. One of the candidates, [68Ga]Ga-HBED-hexadiyne-tropane, showed an IC50 value of 66 nM, together with a log D7.4 of 0.96. A μPET study in a hemi-parkinsonian rat model showed a fast wash-out of the tracer, and no specific uptake in the brain, thus implying an inability to penetrate the BBB.

Synthesis and monoamine uptake inhibition of conformationally constrained 2β-carbomethoxy-3β-phenyl tropanes

A series of 2β-carbomethoxy-3β-phenyl tropanes with conformationally constrained nitrogen substituents were synthesized as potential selective dopamine transporter ligands. These novel compounds were examined for their monoamine uptake inhibition potency at the human dopamine transporter (hDAT), the human serotonin transporter (hSERT) and the human noradrenalin transporter (hNET), stably expressed in human embryonic kidney cells (HEK). A SAR-study was conducted to determine the contribution of extended, 4-fluorinated, conformationally constrained C4 chains at the tropane nitrogen to human monoamine transporter affinity and selectivity. The Royal Society of Chemistry 2009.

[11C]PR04.MZ, a promising DAT ligand for low concentration imaging: Synthesis, efficient 11C-O-methylation and initial small animal PET studies

PR04.MZ was designed as a highly selective dopamine transporter inhibitor, derived from natural cocaine. Its binding profile indicates that [11C]PR04.MZ may be suited as a PET radioligand for the non-invasive exploration of striatal and extrastriatal DAT populations. As a key feature, its structural design facilitates both, labelling with fluorine-18 at its terminally fluorinated butynyl moiety and carbon-11 at its methyl ester function. The present report concerns the efficient [11C]MeI mediated synthesis of [11C]PR04.MZ from an O-desmethyl precursor trifluoroacetic acid salt with Rb2CO3 in DMF in up to 95 ± 5% labelling yield. A preliminary μPET-experiment demonstrates the reversible, highly specific binding of [11C]PR04.MZ in the brain of a male Sprague-Dawley rat.

METHOD OF FLUORINE-18 LABELLING OF TROPANE DERIVATIVES

The invention relates to a one-step [18F]radiolabelling process of tropanamine derivatives which are useful for imaging the neuronal dopamine transporter (DAT) with Positron Emission Tomography (PET).

Synthesis and biological evaluation of a series of novel N- or O-fluoroalkyl derivatives of tropane: Potential positron emission tomography (PET) imaging agents for the dopamine transporter

A series of novel fluoroalkyl-containing tropane derivatives was synthesized, and their binding affinities for the dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET) were determined via competitive binding assays. Among these derivatives, the fluoropropyl ester of β-CIT (19), the fluoroethyl ester of β-CIT (20), the N-fluoropropyl derivative of β-CBT (12), and the fluoropropyl ester of β-CMT (18) displayed higher affinity and greater selectivity for the DAT versus SERT and NET than FP-CIT, which indicates that they are attractive candidates for the development of 18F-labeled PET imaging agents for the DAT.

Synthesis and binding affinities of 2β-(3-iodoallyloxycarbonyl)-3β-(4-substituted-aryl)tropane analogues as ligands for the dopamine transporter studies

Tropane analogues from cocaine, which is known to be one of the most reinforcing and addictive compounds, were designed, synthesized, and characterized for inhibition of presynaptic uptake of dopamine (DA) in brain. Eight new derivatives of 3β-aryl-2β-(3-iodoallyloxycarbonyl)tropanes were synthesized and tested for their potential abilities to displace [3H]2β-carbomethoxy-3β-(4-fluorophenyl)tropane (WIN 35,428) binding to the rat striatal membranes.

Synthesis of [11C]2β-Carbomethoxy-3β-(3'-iodo-4'-methyl, -ethyl and isopropyl Phenyl)Nortropane as Potential Radiotracers for Examination of the Serotonin Transporter with Positron Emission Tomography

Research on depression and anxiety disorders would benefit from the development of suitable radioligands for PET-imaging of the serotonin transporter. Three cocaine analogues, 2β-carbomethoxy-3β-(3'-iodo-4'-methyl, -ethyl and isopropyl phenyl)nortropane (LBT-14, EINT and LBT-44), were prepared in a three-step synthesis by 1-4 addition of the appropriate Grignard reagent to anhydroecgonine methyl ester as first step. lodination of the phenyl ring was accomplished with a mixture of yellow mercuric oxide, perchloric acid and acetic acid followed by a solution of iodine in dichloromethane. N-desmethylation was performed by using 2,2,2-trichloroethylchloroformiate followed by treatment of zinc in acetic acid. Acidic hydrolysis of the ester functions gave the carboxylic acid analogues of LBT-14, EINT and LBT-44. The precursors were labelled with 11C using [11C]methyl iodide or [11C]methyl triflate in dimethyl formamide (DMF) and tetrabutyl ammonium hydroxide (TBAH) as base. [11C]LBT-14, [11C]EINT and [11C]LBT-44 were all examined in Cynomolgus monkey with PET. All three compounds entered the monkey brain to a high degree (ca. 5-10 percent of injected dose). There was a marked uptake of radioactivity in the thalamus and the brainstem, regions known to contain serotonin transporters. Pre-treatment with the selective serotonin transporter inhibitor citalopram had minor effect on the binding ratios, suggesting that none of the three examined radioligands are preferable to the previously examined non-iodinated 4'-isopropenyl analogue [11C]RTI-357 for the study of the serotonin reuptake system with PET.

Design, synthesis and biological evaluation of 7-azatricyclodecanes: Analogues of cocaine

The synthesis and biological activity of a series of azatricyclodecane analogues of cocaine are described. All compounds studied in this series exhibit nanomolar potency and good selectivity for the serotonin transporter versus the dopamine transporter. (

Stereoselective synthesis of 2β-carbomethoxy-3β-phenyltropane derivatives. Enhanced stereoselectivity observed for the conjugate addition reaction of phenylmagnesium bromide derivatives with anhydro dichloromethane

The use of dichloromethane as a solvent for the conjugate addition reaction of preformed etheral solutions of phenylmagnesium bromide derivatives with anhydroecgonine methyl ester (2) was found to enhance the stereoselectivity of the reaction and provide the 2β-carbemethoxy-3β-phenyltropane derivatives 3a-d in high yield.