Synthesis of Stable Isotope Labeled Chloroquine, Amodiaquine and Their Metabolites

Wu, Ruilian; Williams, Robert F.; Silks, III, Louis A. “Pete”; Schmidt, Jurgen G.

doi:10.1002/jlcr.3721

Title: Synthesis of Stable Isotope Labeled Chloroquine, Amodiaquine and Their Metabolites

Abstract

Anti–malaria drugs chloroquine, amodiaquine and their metabolites were stable isotope labeled with ¹³C and 15N starting from uniformly ¹³C labeled benzene and ¹⁵N labeled potassium nitrate to give M+7 isotopomers. Here, chloroquine, and its metabolites were prepared from 7–chloro–1,2,3,4–tetrahydroquinolin–4–one through addition to the carbonyl with the corresponding amines; and the amodiaquine and its metabolites were prepared from 4,7–dichloroquinoline in a selective aryl–halogen exchange with the corresponding amines.

Authors:

^[1];

^[1]

Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

Publication Date:: 2019-03-18

Research Org.:: Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

Sponsoring Org.:: USDOE

OSTI Identifier:: 1511624

Report Number(s):: LA-UR-18-31663
Journal ID: ISSN 0362-4803

Grant/Contract Number:: 89233218CNA000001

Resource Type:: Accepted Manuscript

Journal Name:: Journal of Labelled Compounds and Radiopharmaceuticals

Additional Journal Information:: Journal Volume: 62; Journal Issue: 5; Journal ID: ISSN 0362-4803

Publisher:: Wiley

Country of Publication:: United States

Language:: English

Subject:: 07 ISOTOPE AND RADIATION SOURCES; chloroquine; amodiaquine; [U-13C]benzene; mass spectral standards

Citation Formats


                    Wu, Ruilian, Williams, Robert F., Silks, III, Louis A. “Pete”, and Schmidt, Jurgen G.. Synthesis of Stable Isotope Labeled Chloroquine, Amodiaquine and Their Metabolites.  United States: N. p., 2019. 
Web.  doi:10.1002/jlcr.3721.

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                    Wu, Ruilian, Williams, Robert F., Silks, III, Louis A. “Pete”, & Schmidt, Jurgen G.. Synthesis of Stable Isotope Labeled Chloroquine, Amodiaquine and Their Metabolites.  United States.  https://doi.org/10.1002/jlcr.3721

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                    Wu, Ruilian, Williams, Robert F., Silks, III, Louis A. “Pete”, and Schmidt, Jurgen G.. Mon .  
"Synthesis of Stable Isotope Labeled Chloroquine, Amodiaquine and Their Metabolites".  United States.  https://doi.org/10.1002/jlcr.3721.  https://www.osti.gov/servlets/purl/1511624.

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@article{osti_1511624,

  title        = {Synthesis of Stable Isotope Labeled Chloroquine, Amodiaquine and Their Metabolites},

  author       = {Wu, Ruilian and Williams, Robert F. and Silks, III, Louis A. “Pete” and Schmidt, Jurgen G.},

  abstractNote = {Anti–malaria drugs chloroquine, amodiaquine and their metabolites were stable isotope labeled with 13C and 15N starting from uniformly 13C labeled benzene and 15N labeled potassium nitrate to give M+7 isotopomers. Here, chloroquine, and its metabolites were prepared from 7–chloro–1,2,3,4–tetrahydroquinolin–4–one through addition to the carbonyl with the corresponding amines; and the amodiaquine and its metabolites were prepared from 4,7–dichloroquinoline in a selective aryl–halogen exchange with the corresponding amines.},

  doi          = {10.1002/jlcr.3721},

  journal      = {Journal of Labelled Compounds and Radiopharmaceuticals},

  number       = 5,

  volume       = 62,

  place        = {United States},

  year         = {2019},

  month        = {3}

}

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Similar Records

Title: Synthesis of Stable Isotope Labeled Chloroquine, Amodiaquine and Their Metabolites

Abstract

Citation Formats

4-Aminoquinolines—Past, present, and future; A chemical perspective journal, January 1998

Trichloroisocyanuric acid in H2SO4: an efficient superelectrophilic reagent for chlorination of isatin and benzene derivatives journal, January 2005

The Lysosomal Protein Saposin B Binds Chloroquine journal, November 2015

New 4-Aminoquinoline Mannich Base Antimalarials. 1. Effect of an Alkyl Substituent in the 5‘-Position of the 4‘-Hydroxyanilino Side Chain journal, July 1999

Synthesis of some novel amodiaquine analogs as potential antimalarial and antifilarial compounds journal, December 1981

Improved syntheses of hydroxy acid precursors of macrolide pheromones of cucujid grain beetles journal, July 1986

Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Amodiaquine Hydrochloride journal, December 2012

A general route for 13 C-labeled fluorenols and phenanthrenols via palladium-catalyzed cross-coupling and one-carbon homologation : A general route for journal, July 2013

Adverse Effects of Antimalarials: An Update journal, January 1993

Proton transfer equilibrium in Schiff bases derived from 5-nitrosalicylaldehyde. a study of deuterium isotope effects on13C NMR chemical shifts journal, April 1999

The Synthesis of 4-Hydroxyquinolines. 1 I. Through Ethoxymethylenemalonic Ester journal, July 1946

Synthesis of 13C labeled sulfur and nitrogen mustard metabolites as mass spectrometry standards for monitoring and detecting chemical warfare agents: Synthesis of 13C labeled surfur and nitrogen mustard metabolites journal, May 2012

Chloroquine Manufacture journal, April 1949

A New Synthesis of Chloroquine journal, September 1952

Some 7-Substituted 4-Aminoquinoline Derivatives journal, January 1946

Nitric acid in dichloromethane solution. Facile preparation from potassium nitrate and sulfuric acid journal, February 2001

Montmorillonite catalyzed reduction of nitroarenes with hydrazine journal, January 1990

4-Aminoquinolines—Past, present, and future; A chemical perspective
journal, January 1998

Trichloroisocyanuric acid in H2SO4: an efficient superelectrophilic reagent for chlorination of isatin and benzene derivatives
journal, January 2005

The Lysosomal Protein Saposin B Binds Chloroquine
journal, November 2015

New 4-Aminoquinoline Mannich Base Antimalarials. 1. Effect of an Alkyl Substituent in the 5‘-Position of the 4‘-Hydroxyanilino Side Chain
journal, July 1999

Synthesis of some novel amodiaquine analogs as potential antimalarial and antifilarial compounds
journal, December 1981

Improved syntheses of hydroxy acid precursors of macrolide pheromones of cucujid grain beetles
journal, July 1986

Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Amodiaquine Hydrochloride
journal, December 2012

A general route for ¹³ C-labeled fluorenols and phenanthrenols via palladium-catalyzed cross-coupling and one-carbon homologation : A general route for
journal, July 2013

Adverse Effects of Antimalarials: An Update
journal, January 1993

Proton transfer equilibrium in Schiff bases derived from 5-nitrosalicylaldehyde. a study of deuterium isotope effects on13C NMR chemical shifts
journal, April 1999

The Synthesis of 4-Hydroxyquinolines. ¹ I. Through Ethoxymethylenemalonic Ester
journal, July 1946

Synthesis of 13C labeled sulfur and nitrogen mustard metabolites as mass spectrometry standards for monitoring and detecting chemical warfare agents: Synthesis of 13C labeled surfur and nitrogen mustard metabolites
journal, May 2012

Chloroquine Manufacture
journal, April 1949

A New Synthesis of Chloroquine
journal, September 1952

Some 7-Substituted 4-Aminoquinoline Derivatives
journal, January 1946

Nitric acid in dichloromethane solution. Facile preparation from potassium nitrate and sulfuric acid
journal, February 2001

Montmorillonite catalyzed reduction of nitroarenes with hydrazine
journal, January 1990