A One-Step, Atom Economical Synthesis of Thieno[2,3-d]pyrimidin-4-amine Derivatives by a Four-Component Reaction

Taoda Shi; Christopher J. Zerio; Jared Sivinski; Andrew J. Ambrose; Kohlson T. Moore; Thomas Buckley; Lynn Kaneko; Mae Zhang; Donna D. Zhang; Eli Chapman

doi:10.1002/ejoc.201900414

A One-Step, Atom Economical Synthesis of Thieno[2,3-d]pyrimidin-4-amine Derivatives by a Four-Component Reaction

Taoda Shi, Christopher J. Zerio, Jared Sivinski, Andrew J. Ambrose, Kohlson T. Moore, Thomas Buckley, Lynn Kaneko, Mae Zhang, Donna D. Zhang, Eli Chapman

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

11 Scopus citations

Abstract

A Na₂HPO₄-catalyzed four-component reaction between a ketone, malononitrile, S₈ and formamide has been realized for the first time. This reaction provides a concise approach to thieno[2,3-d]pyrimidin-4-amines, previously requiring 5 steps. The utility of this reaction was validated by preparing a multi-targeted kinase inhibitor and an inhibitor of the NRF2 pathway with excellent atom- and step-economy.

Original language	English (US)
Pages (from-to)	3269-3272
Number of pages	4
Journal	European Journal of Organic Chemistry
Volume	2019
Issue number	20
DOIs	https://doi.org/10.1002/ejoc.201900414
State	Published - Jun 2 2019

Keywords

Atom economy
Multi-component reaction
Organocatalysis
Structural diversity
Thieno[2,3-d]pyrimidin-4-amines

ASJC Scopus subject areas

Physical and Theoretical Chemistry
Organic Chemistry

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10.1002/ejoc.201900414

Cite this

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title = "A One-Step, Atom Economical Synthesis of Thieno[2,3-d]pyrimidin-4-amine Derivatives by a Four-Component Reaction",

abstract = "A Na2HPO4-catalyzed four-component reaction between a ketone, malononitrile, S8 and formamide has been realized for the first time. This reaction provides a concise approach to thieno[2,3-d]pyrimidin-4-amines, previously requiring 5 steps. The utility of this reaction was validated by preparing a multi-targeted kinase inhibitor and an inhibitor of the NRF2 pathway with excellent atom- and step-economy.",

keywords = "Atom economy, Multi-component reaction, Organocatalysis, Structural diversity, Thieno[2,3-d]pyrimidin-4-amines",

author = "Taoda Shi and Zerio, {Christopher J.} and Jared Sivinski and Ambrose, {Andrew J.} and Moore, {Kohlson T.} and Thomas Buckley and Lynn Kaneko and Mae Zhang and Zhang, {Donna D.} and Eli Chapman",

note = "Funding Information: This work was supported by NIH grant ES023758 to E. C. and D. D. Z. Publisher Copyright: {\textcopyright} 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim",

year = "2019",

month = jun,

day = "2",

doi = "10.1002/ejoc.201900414",

language = "English (US)",

volume = "2019",

pages = "3269--3272",

journal = "European Journal of Organic Chemistry",

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T1 - A One-Step, Atom Economical Synthesis of Thieno[2,3-d]pyrimidin-4-amine Derivatives by a Four-Component Reaction

AU - Shi, Taoda

AU - Zerio, Christopher J.

AU - Sivinski, Jared

AU - Ambrose, Andrew J.

AU - Moore, Kohlson T.

AU - Buckley, Thomas

AU - Kaneko, Lynn

AU - Zhang, Mae

AU - Zhang, Donna D.

AU - Chapman, Eli

PY - 2019/6/2

Y1 - 2019/6/2

N2 - A Na2HPO4-catalyzed four-component reaction between a ketone, malononitrile, S8 and formamide has been realized for the first time. This reaction provides a concise approach to thieno[2,3-d]pyrimidin-4-amines, previously requiring 5 steps. The utility of this reaction was validated by preparing a multi-targeted kinase inhibitor and an inhibitor of the NRF2 pathway with excellent atom- and step-economy.

AB - A Na2HPO4-catalyzed four-component reaction between a ketone, malononitrile, S8 and formamide has been realized for the first time. This reaction provides a concise approach to thieno[2,3-d]pyrimidin-4-amines, previously requiring 5 steps. The utility of this reaction was validated by preparing a multi-targeted kinase inhibitor and an inhibitor of the NRF2 pathway with excellent atom- and step-economy.

KW - Atom economy

KW - Multi-component reaction

KW - Organocatalysis

KW - Structural diversity

KW - Thieno[2,3-d]pyrimidin-4-amines

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DO - 10.1002/ejoc.201900414

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JF - European Journal of Organic Chemistry

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A One-Step, Atom Economical Synthesis of Thieno[2,3-d]pyrimidin-4-amine Derivatives by a Four-Component Reaction

Abstract

Keywords

ASJC Scopus subject areas

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CCDC 1904050: Experimental Crystal Structure Determination

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A One-Step, Atom Economical Synthesis of Thieno[2,3-d]pyrimidin-4-amine Derivatives by a Four-Component Reaction

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

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Datasets

CCDC 1904050: Experimental Crystal Structure Determination

Cite this