Synthesis of 8-Fluoro-3,4-dihydroisoquinoline and Its Transformation to 1,8-Disubstituted Tetrahydroisoquinolines

A simple procedure for the synthesis of 8-fluoro-3,4-dihydroisoquinoline is described below, based on a directed ortho-lithiation reaction. This key intermediate was then applied in various transformations. Fluorine–amine exchange afforded the corresponding 8-amino-3,4-dihydroisoquinolines...

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Main Authors:	Csilla Hargitai, Tamás Nagy, Judit Halász, Gyula Simig, Balázs Volk
Format:	Article
Language:	English
Published:	MDPI AG 2018-05-01
Series:	Molecules
Subjects:	isoquinoline lithiation nucleophilic aromatic substitution reduction alkylation cyclization
Online Access:	http://www.mdpi.com/1420-3049/23/6/1280

id	doaj-7e16f855fadc4f29a154bc3632cd59b0
record_format	Article
spelling	doaj-7e16f855fadc4f29a154bc3632cd59b02020-11-24T21:09:56ZengMDPI AGMolecules1420-30492018-05-01236128010.3390/molecules23061280molecules23061280Synthesis of 8-Fluoro-3,4-dihydroisoquinoline and Its Transformation to 1,8-Disubstituted TetrahydroisoquinolinesCsilla Hargitai0Tamás Nagy1Judit Halász2Gyula Simig3Balázs Volk4Directorate of Drug Substance Development, Egis Pharmaceuticals Plc., P.O. Box 100, H-1475 Budapest, HungaryDirectorate of Drug Substance Development, Egis Pharmaceuticals Plc., P.O. Box 100, H-1475 Budapest, HungaryDirectorate of Drug Substance Development, Egis Pharmaceuticals Plc., P.O. Box 100, H-1475 Budapest, HungaryDirectorate of Drug Substance Development, Egis Pharmaceuticals Plc., P.O. Box 100, H-1475 Budapest, HungaryDirectorate of Drug Substance Development, Egis Pharmaceuticals Plc., P.O. Box 100, H-1475 Budapest, HungaryA simple procedure for the synthesis of 8-fluoro-3,4-dihydroisoquinoline is described below, based on a directed ortho-lithiation reaction. This key intermediate was then applied in various transformations. Fluorine–amine exchange afforded the corresponding 8-amino-3,4-dihydroisoquinolines, suitable starting compounds for the synthesis of 1-substituted 8-amino-tetrahydroisoquinolines. On the other hand, reduction and alkylation reactions of 8-fluoro-3,4-dihydroisoquinoline led to novel 1,2,3,4-tetrahydroisoquinoline derivatives that can be used as building blocks in the synthesis of potential central nervous system drug candidates.http://www.mdpi.com/1420-3049/23/6/1280isoquinolinelithiationnucleophilic aromatic substitutionreductionalkylationcyclization
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Csilla Hargitai Tamás Nagy Judit Halász Gyula Simig Balázs Volk
spellingShingle	Csilla Hargitai Tamás Nagy Judit Halász Gyula Simig Balázs Volk Synthesis of 8-Fluoro-3,4-dihydroisoquinoline and Its Transformation to 1,8-Disubstituted Tetrahydroisoquinolines Molecules isoquinoline lithiation nucleophilic aromatic substitution reduction alkylation cyclization
author_facet	Csilla Hargitai Tamás Nagy Judit Halász Gyula Simig Balázs Volk
author_sort	Csilla Hargitai
title	Synthesis of 8-Fluoro-3,4-dihydroisoquinoline and Its Transformation to 1,8-Disubstituted Tetrahydroisoquinolines
title_short	Synthesis of 8-Fluoro-3,4-dihydroisoquinoline and Its Transformation to 1,8-Disubstituted Tetrahydroisoquinolines
title_full	Synthesis of 8-Fluoro-3,4-dihydroisoquinoline and Its Transformation to 1,8-Disubstituted Tetrahydroisoquinolines
title_fullStr	Synthesis of 8-Fluoro-3,4-dihydroisoquinoline and Its Transformation to 1,8-Disubstituted Tetrahydroisoquinolines
title_full_unstemmed	Synthesis of 8-Fluoro-3,4-dihydroisoquinoline and Its Transformation to 1,8-Disubstituted Tetrahydroisoquinolines
title_sort	synthesis of 8-fluoro-3,4-dihydroisoquinoline and its transformation to 1,8-disubstituted tetrahydroisoquinolines
publisher	MDPI AG
series	Molecules
issn	1420-3049
publishDate	2018-05-01
description	A simple procedure for the synthesis of 8-fluoro-3,4-dihydroisoquinoline is described below, based on a directed ortho-lithiation reaction. This key intermediate was then applied in various transformations. Fluorine–amine exchange afforded the corresponding 8-amino-3,4-dihydroisoquinolines, suitable starting compounds for the synthesis of 1-substituted 8-amino-tetrahydroisoquinolines. On the other hand, reduction and alkylation reactions of 8-fluoro-3,4-dihydroisoquinoline led to novel 1,2,3,4-tetrahydroisoquinoline derivatives that can be used as building blocks in the synthesis of potential central nervous system drug candidates.
topic	isoquinoline lithiation nucleophilic aromatic substitution reduction alkylation cyclization
url	http://www.mdpi.com/1420-3049/23/6/1280
work_keys_str_mv	AT csillahargitai synthesisof8fluoro34dihydroisoquinolineanditstransformationto18disubstitutedtetrahydroisoquinolines AT tamasnagy synthesisof8fluoro34dihydroisoquinolineanditstransformationto18disubstitutedtetrahydroisoquinolines AT judithalasz synthesisof8fluoro34dihydroisoquinolineanditstransformationto18disubstitutedtetrahydroisoquinolines AT gyulasimig synthesisof8fluoro34dihydroisoquinolineanditstransformationto18disubstitutedtetrahydroisoquinolines AT balazsvolk synthesisof8fluoro34dihydroisoquinolineanditstransformationto18disubstitutedtetrahydroisoquinolines
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Synthesis of 8-Fluoro-3,4-dihydroisoquinoline and Its Transformation to 1,8-Disubstituted Tetrahydroisoquinolines

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