Synthesis of [²H₇]indatraline

Abstract

Deuterium-labelled indatraline was synthesized in high efficiency employing a Friedel-Crafts alkylation of [(2)H6]benzene with (E)-3-(3,4-dichlorophenyl)acrylic acid as a key step. The desired labelling of the final compound was ascertained in two ways, by incorporation of [(2)H6]benzene in the target molecule and additionally by deuterium transfer to the non-deuterated aryl moiety of the Friedel-Crafts alkylation product from [(2)H6]benzene, the latter thus serving as reagent and solvent.

MS Binding Assays for the Three Monoamine Transporters Using the Triple Reuptake Inhibitor (1R,3S)‐Indatraline as Native Marker

“…HPLC‐grade (NH 4 )OAc and HEPES were purchased from VWR Prolabo. The hydrochloride of indatraline [ rac ‐(1 R ,3 S )‐ 1 ],10 the deuterochloride of rac ‐(1 R ,3 S )( 2 H 7 )‐indatraline [ rac ‐(1 R ,3 S )( 2 H 7 )‐ 1 ],20 and the hydrochloride of the cis ‐configured diastereomer [ rac ‐(1 R ,3 R )‐ 2 ]9 were synthesized in house according to published methods. The hydrochlorides of the pure enantiomers (1 R ,3 S )‐indatraline [(1 R ,3 S )‐ 1 ] and (1 S ,3 R )‐indatraline [(1 S ,3 R )‐ 1 ] possessed an enantiomeric purity of >99.75 % ee and >99.67 % ee , respectively, determined according to the method previously described 10.…”

Development and validation of an LC‐ESI‐MS/MS method for the quantification of D‐84, reboxetine and citalopram for their use in MS Binding Assays addressing the monoamine transporters hDAT, hSERT and hNET

“…Enantiomeric excesses amounted to ≥99.8% for ( R , R )‐D‐84 [( R , R )‐ 1 ] and 99.3% for ( S , S )‐reboxetine [( S , S )‐ 2 ]. [ 2 H 4 ]‐4‐(2‐benzhydryloxyethyl)‐1‐(4‐fluorobenzyl)piperidin‐3‐ol ( rac ‐[ 2 H 4 ]‐D‐84, rac ‐[ 2 H 4 ]‐ 1 ) was synthesized utilizing an H/D exchange reaction; the chemical purity was 99.2% (Allmendinger & Wanner, ; total synthesis is to be published soon). rac ‐[ 2 H 3 ]‐Indatraline ( rac ‐[ 2 H 3 ]‐ 4 ) HCl was synthesized according to Grimm et al (; for synthesis see Supporting Information).…”