Acid-facilitated debenzylation of N-Boc, N-benzyl double protected 2-aminopyridinomethyl pyrrolidine derivatives

Haitao Ji; Qing Jing; Jinwen Huang; Richard B. Silverman

doi:10.1016/j.tet.2011.12.013

Acid-facilitated debenzylation of N-Boc, N-benzyl double protected 2-aminopyridinomethyl pyrrolidine derivatives

Haitao Ji, Qing Jing, Jinwen Huang, Richard B. Silverman^*

^*Corresponding author for this work

Chemistry

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

17 Scopus citations

Abstract

2-Aminopyridinomethyl pyrrolidines represent a class of highly potent and selective neuronal nitric oxide synthase inhibitors. Conditions for a Mitsunobu reaction of a naphthol and a hindered secondary alcohol were optimized to give good to excellent yields. A key step in the synthesis of these inhibitors is the deprotection of the benzyl group from the N-Boc and N-Bn double protected 2-aminopyridine ring at a late stage of the synthesis, which has been proven difficult in our previous syntheses. Acetic acid was found to facilitate the N-Bn deprotection.

Original language	English (US)
Pages (from-to)	1359-1366
Number of pages	8
Journal	Tetrahedron
Volume	68
Issue number	5
DOIs	https://doi.org/10.1016/j.tet.2011.12.013
State	Published - Feb 4 2012

Funding

The authors are grateful to the National Institutes of Health ( GM049725 ) for financial support of this research.

Keywords

2-Aminopyridinomethyl pyrrolidines
Mitsunobu reaction
N-Benzyl deprotection
Palladium-catalyzed hydrogenation

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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10.1016/j.tet.2011.12.013

Cite this

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title = "Acid-facilitated debenzylation of N-Boc, N-benzyl double protected 2-aminopyridinomethyl pyrrolidine derivatives",

abstract = "2-Aminopyridinomethyl pyrrolidines represent a class of highly potent and selective neuronal nitric oxide synthase inhibitors. Conditions for a Mitsunobu reaction of a naphthol and a hindered secondary alcohol were optimized to give good to excellent yields. A key step in the synthesis of these inhibitors is the deprotection of the benzyl group from the N-Boc and N-Bn double protected 2-aminopyridine ring at a late stage of the synthesis, which has been proven difficult in our previous syntheses. Acetic acid was found to facilitate the N-Bn deprotection.",

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note = "Funding Information: The authors are grateful to the National Institutes of Health ( GM049725 ) for financial support of this research. ",

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AU - Ji, Haitao

AU - Jing, Qing

AU - Huang, Jinwen

AU - Silverman, Richard B.

N1 - Funding Information: The authors are grateful to the National Institutes of Health ( GM049725 ) for financial support of this research.

PY - 2012/2/4

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AB - 2-Aminopyridinomethyl pyrrolidines represent a class of highly potent and selective neuronal nitric oxide synthase inhibitors. Conditions for a Mitsunobu reaction of a naphthol and a hindered secondary alcohol were optimized to give good to excellent yields. A key step in the synthesis of these inhibitors is the deprotection of the benzyl group from the N-Boc and N-Bn double protected 2-aminopyridine ring at a late stage of the synthesis, which has been proven difficult in our previous syntheses. Acetic acid was found to facilitate the N-Bn deprotection.

KW - 2-Aminopyridinomethyl pyrrolidines

KW - Mitsunobu reaction

KW - N-Benzyl deprotection

KW - Palladium-catalyzed hydrogenation

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JF - Tetrahedron

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Acid-facilitated debenzylation of N-Boc, N-benzyl double protected 2-aminopyridinomethyl pyrrolidine derivatives

Abstract

Funding

Keywords

ASJC Scopus subject areas

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