Synthesis of tetrazolo-fused benzodiazepines and benzodiazepinones by a two-step protocol using an Ugi-azide reaction for initial diversity generation

Steven Gunawan; Muhammad Ayaz; Fabio De Moliner; Brendan Frett; Christine Kaiser; Nina Patrick; Zhigang Xu; Christopher Hulme

doi:10.1016/j.tet.2012.04.068

Synthesis of tetrazolo-fused benzodiazepines and benzodiazepinones by a two-step protocol using an Ugi-azide reaction for initial diversity generation

Steven Gunawan
, Muhammad Ayaz
, Fabio De Moliner
, Brendan Frett
, Christine Kaiser
, Nina Patrick
, Zhigang Xu
, Christopher Hulme

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

52 Scopus citations

Abstract

A two-step strategy for the synthesis of arrays of tricyclic tetrazolo-fused benzodiazepines and benzodiazepinones has been investigated. The protocol uses ortho-N-Boc phenylisocyanides and phenylglyoxaldehydes or ethyl glyoxylate in the four-component Ugi-azide reaction to afford MCR (MultiComponent Reactions) derived adducts equipped with the desired diversity inputs. A subsequent acidic treatment (TFA/DCE) allows a simultaneous deprotection-cyclization leading to the final products.

Original language	English (US)
Pages (from-to)	5606-5611
Number of pages	6
Journal	Tetrahedron
Volume	68
Issue number	27-28
DOIs	https://doi.org/10.1016/j.tet.2012.04.068
State	Published - Jul 8 2012

Keywords

Benzodiazepines
Benzodiazepinones
TMS-N
Tetrazoles
Ugi reaction

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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10.1016/j.tet.2012.04.068

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title = "Synthesis of tetrazolo-fused benzodiazepines and benzodiazepinones by a two-step protocol using an Ugi-azide reaction for initial diversity generation",

abstract = "A two-step strategy for the synthesis of arrays of tricyclic tetrazolo-fused benzodiazepines and benzodiazepinones has been investigated. The protocol uses ortho-N-Boc phenylisocyanides and phenylglyoxaldehydes or ethyl glyoxylate in the four-component Ugi-azide reaction to afford MCR (MultiComponent Reactions) derived adducts equipped with the desired diversity inputs. A subsequent acidic treatment (TFA/DCE) allows a simultaneous deprotection-cyclization leading to the final products.",

keywords = "Benzodiazepines, Benzodiazepinones, TMS-N, Tetrazoles, Ugi reaction",

author = "Steven Gunawan and Muhammad Ayaz and \{De Moliner\}, Fabio and Brendan Frett and Christine Kaiser and Nina Patrick and Zhigang Xu and Christopher Hulme",

note = "Funding Information: The authors thank Kristen Keck for compound purification, Alex Laetsch for compound management, Gary Nichol for X-ray crystallographic work, and Nicole Schechter for proof-reading. National Institute of Health (NIH) is gratefully acknowledged for funding ( P41GM086190 ). ",

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doi = "10.1016/j.tet.2012.04.068",

language = "English (US)",

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AU - Gunawan, Steven

AU - Ayaz, Muhammad

AU - De Moliner, Fabio

AU - Frett, Brendan

AU - Kaiser, Christine

AU - Patrick, Nina

AU - Xu, Zhigang

AU - Hulme, Christopher

N1 - Funding Information: The authors thank Kristen Keck for compound purification, Alex Laetsch for compound management, Gary Nichol for X-ray crystallographic work, and Nicole Schechter for proof-reading. National Institute of Health (NIH) is gratefully acknowledged for funding ( P41GM086190 ).

PY - 2012/7/8

Y1 - 2012/7/8

N2 - A two-step strategy for the synthesis of arrays of tricyclic tetrazolo-fused benzodiazepines and benzodiazepinones has been investigated. The protocol uses ortho-N-Boc phenylisocyanides and phenylglyoxaldehydes or ethyl glyoxylate in the four-component Ugi-azide reaction to afford MCR (MultiComponent Reactions) derived adducts equipped with the desired diversity inputs. A subsequent acidic treatment (TFA/DCE) allows a simultaneous deprotection-cyclization leading to the final products.

AB - A two-step strategy for the synthesis of arrays of tricyclic tetrazolo-fused benzodiazepines and benzodiazepinones has been investigated. The protocol uses ortho-N-Boc phenylisocyanides and phenylglyoxaldehydes or ethyl glyoxylate in the four-component Ugi-azide reaction to afford MCR (MultiComponent Reactions) derived adducts equipped with the desired diversity inputs. A subsequent acidic treatment (TFA/DCE) allows a simultaneous deprotection-cyclization leading to the final products.

KW - Benzodiazepines

KW - Benzodiazepinones

KW - TMS-N

KW - Tetrazoles

KW - Ugi reaction

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UR - https://www.scopus.com/pages/publications/84861998944#tab=citedBy

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DO - 10.1016/j.tet.2012.04.068

M3 - Article

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SN - 0040-4020

VL - 68

SP - 5606

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JO - Tetrahedron

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IS - 27-28

ER -

Synthesis of tetrazolo-fused benzodiazepines and benzodiazepinones by a two-step protocol using an Ugi-azide reaction for initial diversity generation

Abstract

Keywords

ASJC Scopus subject areas

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