Rapid, microwave-assisted organic synthesis of selective V600EBRAF inhibitors for preclinical cancer research

Jason R. Buck; Sam Saleh; Md Imam Uddin; H. Charles Manning

doi:10.1016/j.tetlet.2012.05.137

Rapid, microwave-assisted organic synthesis of selective ^V600EBRAF inhibitors for preclinical cancer research

Jason R. Buck, Sam Saleh, Md Imam Uddin, H. Charles Manning

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

17 Scopus citations

Abstract

We report dramatically improved total syntheses of two highly selective ^V600EBRAF inhibitors, PLX4720 and PLX4032, that leverages microwave-assisted organic synthesis (MAOS). Compared with previously reported approaches, our novel MAOS method significantly reduces overall reaction time without compromising yield. In addition to providing a gram-scale route to these compounds for preclinical oncology research, we anticipate this approach could accelerate the synthesis of azaindoles in high-throughput, library-based formats.

Original language	English (US)
Pages (from-to)	4161-4165
Number of pages	5
Journal	Tetrahedron Letters
Volume	53
Issue number	32
DOIs	https://doi.org/10.1016/j.tetlet.2012.05.137
State	Published - Aug 8 2012
Externally published	Yes

Keywords

BRAF
MAOS
Melanoma
PLX4032
PLX4720

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

Access to Document

10.1016/j.tetlet.2012.05.137

Cite this

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title = "Rapid, microwave-assisted organic synthesis of selective V600EBRAF inhibitors for preclinical cancer research",

abstract = "We report dramatically improved total syntheses of two highly selective V600EBRAF inhibitors, PLX4720 and PLX4032, that leverages microwave-assisted organic synthesis (MAOS). Compared with previously reported approaches, our novel MAOS method significantly reduces overall reaction time without compromising yield. In addition to providing a gram-scale route to these compounds for preclinical oncology research, we anticipate this approach could accelerate the synthesis of azaindoles in high-throughput, library-based formats.",

keywords = "BRAF, MAOS, Melanoma, PLX4032, PLX4720",

author = "Buck, {Jason R.} and Sam Saleh and {Imam Uddin}, Md and Manning, {H. Charles}",

note = "Funding Information: The authors wish to gratefully acknowledge funding from the National Cancer Institute (NCI): 1R01 CA140628, 1RC1 CA145138-01, K25 CA127349, 1P50 CA128323 (Vanderbilt ICMIC Program), 2P50 CA095103 (Vanderbilt SPORE in GI Cancer), 5P30 DK058404, and the Kleberg Foundation. The authors wish to thank Dr. Yiu-Yin Cheung for helpful discussions. ",

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doi = "10.1016/j.tetlet.2012.05.137",

language = "English (US)",

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AU - Buck, Jason R.

AU - Saleh, Sam

AU - Imam Uddin, Md

AU - Manning, H. Charles

N1 - Funding Information: The authors wish to gratefully acknowledge funding from the National Cancer Institute (NCI): 1R01 CA140628, 1RC1 CA145138-01, K25 CA127349, 1P50 CA128323 (Vanderbilt ICMIC Program), 2P50 CA095103 (Vanderbilt SPORE in GI Cancer), 5P30 DK058404, and the Kleberg Foundation. The authors wish to thank Dr. Yiu-Yin Cheung for helpful discussions.

PY - 2012/8/8

Y1 - 2012/8/8

N2 - We report dramatically improved total syntheses of two highly selective V600EBRAF inhibitors, PLX4720 and PLX4032, that leverages microwave-assisted organic synthesis (MAOS). Compared with previously reported approaches, our novel MAOS method significantly reduces overall reaction time without compromising yield. In addition to providing a gram-scale route to these compounds for preclinical oncology research, we anticipate this approach could accelerate the synthesis of azaindoles in high-throughput, library-based formats.

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