Synthesis of new 1-Aryl-4-(biarylmethylene)piperazine ligands, structurally related to adoprazine (SLV313)

Nisar Ullah

doi:10.1515/znb-2012-0113

Synthesis of new 1-Aryl-4-(biarylmethylene)piperazine ligands, structurally related to adoprazine (SLV313)

Nisar Ullah^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

A series of new 1-aryl-4-(biarylmethylene)piperazines has been synthesized. These ligands are structurally related to SLV-313, a potential atypical antipsychotic having potent D₂ receptor antagonist and 5-HT _1A receptor agonist properties. Buchwald-Hartwig coupling reactions of 1-boc-piperazine with appropriate aryl halides and subsequent removal of the boc group rendered arylpiperazines. The reductive amination of the latter with suitable biarylaldehydes accomplished the synthesis of these ligands.

Original language	English
Pages (from-to)	75-84
Number of pages	10
Journal	Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences
Volume	67
Issue number	1
DOIs	https://doi.org/10.1515/znb-2012-0113
State	Published - Jan 2012

Bibliographical note

Funding Information:
Following the same procedure as adopted for the synthesis of 3a, the title compound was obtained as a light-yellow solid from compounds 5 and 6f (52 %). M. p. 103 – 105 ◦C. – IR (neat): ν = 3052, 3033, 2980, 2972, 2970, 1682, 1633, 1541, 1426 cm−1. – 1H NMR (CDCl3, 500 MHz): δ = 2.05 (m, 2 H, cyclopent H), 2.55 (m, 2 H, cyclopent H), 2.62 (m, 2 H, 4-H), 2.63 – 2.70 (br. s, 4 H, piperazine H), 2.72 (m, 2 H, cyclopent H), 2.88 (br. s, 4 H, piperazine H), 2.97 (m, 2 H, 3-H), 3.59 (NCH2Ar), 6.31 (s, 1 H, cyclopent H), 6.95 (m, 2 H, 6-H, 7-H), 7.05 (dd, J = 2.5, 6.8 Hz, 1 H, 5-H), 7.69 (br. s, 1 H, 4′-H), 8.12 (br. s, 1 H, NHCO), 8.42 (s, 1 H, 2′-H), 8.60 (s, 1 H, 6′-H). – 13C NMR (CDCl3, 125.7 MHz): δ = 23.13 (Ccyclopent), 25.44 (C-4), 30.61 (C-3), 32.86 (Ccyclopent), 33.34 (Ccyclopent), 51.98 (Cpiper), 53.35 (Cpiper), 60.13 (NCH2Ar), 119.37, 122.80, 123.84, 123.99, 128.45, 132.03, 132.12, 132.66, 133.39, 138.80, 139.27, 145.85, 148.35 (all Carom), 170.47 (C-2). – C24H28N4O (388.51): calcd. C 74.20, H 7.26, N 14.42; found C 74.13, H 7.30, N 14.34. Acknowledgements Financial support from KACST Project No: AR-28-38 and lab facilities from KFUPM are gratefully acknowledged.

Keywords

Aryl-(biarylmethylene)piperazines
Buchwald-Hartwig amination
Reductive amination
Schizophrenia

ASJC Scopus subject areas

General Chemistry

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10.1515/znb-2012-0113

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@article{4971808204c54979b8e97bb559fae801,

title = "Synthesis of new 1-Aryl-4-(biarylmethylene)piperazine ligands, structurally related to adoprazine (SLV313)",

abstract = "A series of new 1-aryl-4-(biarylmethylene)piperazines has been synthesized. These ligands are structurally related to SLV-313, a potential atypical antipsychotic having potent D2 receptor antagonist and 5-HT 1A receptor agonist properties. Buchwald-Hartwig coupling reactions of 1-boc-piperazine with appropriate aryl halides and subsequent removal of the boc group rendered arylpiperazines. The reductive amination of the latter with suitable biarylaldehydes accomplished the synthesis of these ligands.",

keywords = "Aryl-(biarylmethylene)piperazines, Buchwald-Hartwig amination, Reductive amination, Schizophrenia",

author = "Nisar Ullah",

note = "Funding Information: Following the same procedure as adopted for the synthesis of 3a, the title compound was obtained as a light-yellow solid from compounds 5 and 6f (52 \%). M. p. 103 {\textendash} 105 ◦C. {\textendash} IR (neat): ν = 3052, 3033, 2980, 2972, 2970, 1682, 1633, 1541, 1426 cm−1. {\textendash} 1H NMR (CDCl3, 500 MHz): δ = 2.05 (m, 2 H, cyclopent H), 2.55 (m, 2 H, cyclopent H), 2.62 (m, 2 H, 4-H), 2.63 {\textendash} 2.70 (br. s, 4 H, piperazine H), 2.72 (m, 2 H, cyclopent H), 2.88 (br. s, 4 H, piperazine H), 2.97 (m, 2 H, 3-H), 3.59 (NCH2Ar), 6.31 (s, 1 H, cyclopent H), 6.95 (m, 2 H, 6-H, 7-H), 7.05 (dd, J = 2.5, 6.8 Hz, 1 H, 5-H), 7.69 (br. s, 1 H, 4′-H), 8.12 (br. s, 1 H, NHCO), 8.42 (s, 1 H, 2′-H), 8.60 (s, 1 H, 6′-H). {\textendash} 13C NMR (CDCl3, 125.7 MHz): δ = 23.13 (Ccyclopent), 25.44 (C-4), 30.61 (C-3), 32.86 (Ccyclopent), 33.34 (Ccyclopent), 51.98 (Cpiper), 53.35 (Cpiper), 60.13 (NCH2Ar), 119.37, 122.80, 123.84, 123.99, 128.45, 132.03, 132.12, 132.66, 133.39, 138.80, 139.27, 145.85, 148.35 (all Carom), 170.47 (C-2). {\textendash} C24H28N4O (388.51): calcd. C 74.20, H 7.26, N 14.42; found C 74.13, H 7.30, N 14.34. Acknowledgements Financial support from KACST Project No: AR-28-38 and lab facilities from KFUPM are gratefully acknowledged.",

year = "2012",

month = jan,

doi = "10.1515/znb-2012-0113",

language = "English",

volume = "67",

pages = "75--84",

journal = "Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences",

issn = "0932-0776",

publisher = "Walter de Gruyter GmbH",

number = "1",

}

TY - JOUR

T1 - Synthesis of new 1-Aryl-4-(biarylmethylene)piperazine ligands, structurally related to adoprazine (SLV313)

AU - Ullah, Nisar

N1 - Funding Information: Following the same procedure as adopted for the synthesis of 3a, the title compound was obtained as a light-yellow solid from compounds 5 and 6f (52 %). M. p. 103 – 105 ◦C. – IR (neat): ν = 3052, 3033, 2980, 2972, 2970, 1682, 1633, 1541, 1426 cm−1. – 1H NMR (CDCl3, 500 MHz): δ = 2.05 (m, 2 H, cyclopent H), 2.55 (m, 2 H, cyclopent H), 2.62 (m, 2 H, 4-H), 2.63 – 2.70 (br. s, 4 H, piperazine H), 2.72 (m, 2 H, cyclopent H), 2.88 (br. s, 4 H, piperazine H), 2.97 (m, 2 H, 3-H), 3.59 (NCH2Ar), 6.31 (s, 1 H, cyclopent H), 6.95 (m, 2 H, 6-H, 7-H), 7.05 (dd, J = 2.5, 6.8 Hz, 1 H, 5-H), 7.69 (br. s, 1 H, 4′-H), 8.12 (br. s, 1 H, NHCO), 8.42 (s, 1 H, 2′-H), 8.60 (s, 1 H, 6′-H). – 13C NMR (CDCl3, 125.7 MHz): δ = 23.13 (Ccyclopent), 25.44 (C-4), 30.61 (C-3), 32.86 (Ccyclopent), 33.34 (Ccyclopent), 51.98 (Cpiper), 53.35 (Cpiper), 60.13 (NCH2Ar), 119.37, 122.80, 123.84, 123.99, 128.45, 132.03, 132.12, 132.66, 133.39, 138.80, 139.27, 145.85, 148.35 (all Carom), 170.47 (C-2). – C24H28N4O (388.51): calcd. C 74.20, H 7.26, N 14.42; found C 74.13, H 7.30, N 14.34. Acknowledgements Financial support from KACST Project No: AR-28-38 and lab facilities from KFUPM are gratefully acknowledged.

PY - 2012/1

Y1 - 2012/1

N2 - A series of new 1-aryl-4-(biarylmethylene)piperazines has been synthesized. These ligands are structurally related to SLV-313, a potential atypical antipsychotic having potent D2 receptor antagonist and 5-HT 1A receptor agonist properties. Buchwald-Hartwig coupling reactions of 1-boc-piperazine with appropriate aryl halides and subsequent removal of the boc group rendered arylpiperazines. The reductive amination of the latter with suitable biarylaldehydes accomplished the synthesis of these ligands.

AB - A series of new 1-aryl-4-(biarylmethylene)piperazines has been synthesized. These ligands are structurally related to SLV-313, a potential atypical antipsychotic having potent D2 receptor antagonist and 5-HT 1A receptor agonist properties. Buchwald-Hartwig coupling reactions of 1-boc-piperazine with appropriate aryl halides and subsequent removal of the boc group rendered arylpiperazines. The reductive amination of the latter with suitable biarylaldehydes accomplished the synthesis of these ligands.

KW - Aryl-(biarylmethylene)piperazines

KW - Buchwald-Hartwig amination

KW - Reductive amination

KW - Schizophrenia

UR - https://www.scopus.com/pages/publications/84857539201

U2 - 10.1515/znb-2012-0113

DO - 10.1515/znb-2012-0113

M3 - Article

AN - SCOPUS:84857539201

SN - 0932-0776

VL - 67

SP - 75

EP - 84

JO - Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences

JF - Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences

IS - 1

ER -

Synthesis of new 1-Aryl-4-(biarylmethylene)piperazine ligands, structurally related to adoprazine (SLV313)

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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