A practical synthesis of 2-((1H-pyrrolo[2,3-b]pyridine-4-yl)methylamino)-5- fluoronicotinic acid

Xin Wang; Ben Zhi; Jean Baum; Ying Chen; Richard Crockett; Liang Huang; Shawn Eisenberg; John Ng; Robert Larsen; Mike Martinelli; Paul Reider

doi:10.1021/jo0602571

A practical synthesis of 2-((1H-pyrrolo[2,3-b]pyridine-4-yl)methylamino)-5- fluoronicotinic acid

Xin Wang, Ben Zhi, Jean Baum, Ying Chen, Richard Crockett, Liang Huang, Shawn Eisenberg, John Ng, Robert Larsen, Mike Martinelli, Paul Reider

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

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Abstract

A practical synthesis of a key pharmaceutical intermediate, 2-[(1H-pyrrolo[2,3-b]pyridine-4-yl)methylamino]-5-fluoronicotinic acid (1), is described. To introduce the aminomethyl moiety of 2 via a palladium-catalyzed cyanation/reduction sequence, a regioselective chlorination of 7-azaindole via the N-oxide was developed. A highly selective monodechlorination of 2,6-dichloro-5-fluoronicotinic acid was discovered to afford the nicotinic acid 3. The two building blocks 2 and 3 were then coupled to complete the preparation of 1.

Original language	English (US)
Pages (from-to)	4021-4023
Number of pages	3
Journal	Journal of Organic Chemistry
Volume	71
Issue number	10
DOIs	https://doi.org/10.1021/jo0602571
State	Published - May 12 2006
Externally published	Yes

All Science Journal Classification (ASJC) codes

Organic Chemistry

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title = "A practical synthesis of 2-((1H-pyrrolo[2,3-b]pyridine-4-yl)methylamino)-5- fluoronicotinic acid",

abstract = "A practical synthesis of a key pharmaceutical intermediate, 2-[(1H-pyrrolo[2,3-b]pyridine-4-yl)methylamino]-5-fluoronicotinic acid (1), is described. To introduce the aminomethyl moiety of 2 via a palladium-catalyzed cyanation/reduction sequence, a regioselective chlorination of 7-azaindole via the N-oxide was developed. A highly selective monodechlorination of 2,6-dichloro-5-fluoronicotinic acid was discovered to afford the nicotinic acid 3. The two building blocks 2 and 3 were then coupled to complete the preparation of 1.",

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language = "English (US)",

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T1 - A practical synthesis of 2-((1H-pyrrolo[2,3-b]pyridine-4-yl)methylamino)-5- fluoronicotinic acid

AU - Wang, Xin

AU - Zhi, Ben

AU - Baum, Jean

AU - Chen, Ying

AU - Crockett, Richard

AU - Huang, Liang

AU - Eisenberg, Shawn

AU - Ng, John

AU - Larsen, Robert

AU - Martinelli, Mike

AU - Reider, Paul

PY - 2006/5/12

Y1 - 2006/5/12

N2 - A practical synthesis of a key pharmaceutical intermediate, 2-[(1H-pyrrolo[2,3-b]pyridine-4-yl)methylamino]-5-fluoronicotinic acid (1), is described. To introduce the aminomethyl moiety of 2 via a palladium-catalyzed cyanation/reduction sequence, a regioselective chlorination of 7-azaindole via the N-oxide was developed. A highly selective monodechlorination of 2,6-dichloro-5-fluoronicotinic acid was discovered to afford the nicotinic acid 3. The two building blocks 2 and 3 were then coupled to complete the preparation of 1.

AB - A practical synthesis of a key pharmaceutical intermediate, 2-[(1H-pyrrolo[2,3-b]pyridine-4-yl)methylamino]-5-fluoronicotinic acid (1), is described. To introduce the aminomethyl moiety of 2 via a palladium-catalyzed cyanation/reduction sequence, a regioselective chlorination of 7-azaindole via the N-oxide was developed. A highly selective monodechlorination of 2,6-dichloro-5-fluoronicotinic acid was discovered to afford the nicotinic acid 3. The two building blocks 2 and 3 were then coupled to complete the preparation of 1.

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A practical synthesis of 2-((1H-pyrrolo[2,3-b]pyridine-4-yl)methylamino)-5- fluoronicotinic acid

Abstract

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