1195768-06-9

Dabrafenib methanesulfonate salt is a selective BRAF V600E inhibitor. Dabrafenib methanesulfonate salt binds to Raf family kinases and inhibits their activity.

ChEBI: A methanesulfonate (mesylate) salt prepared from equimolar amounts of dabrafenib and methanesulfonic acid. Used for treatment of metastatic melanoma.

Commercially available fluoroaniline 40 was first converted to sulfonamide 42 in 91% yield by treatment with 2,5-difluorobenzenesulfonyl chloride (41) in the presence of pyridine. Next, deprotonation of 2-chloro-4-methylpyrimidine (43) with lithium bis(trimethylsilyl)amide (LHMDS) followed by addition to ester 42 afforded chloropyrimidine 44 in 72% yield. Bromination followed by thiazole formation through the use of 2,2-dimethylpropanethioamide gave the penultimate target 45 in 80% over two steps. Chloropyrimidine 45 was subjected to SNAr conditions with ammonium hydroxide to furnish the aminopyrimidine in 88% yield, and this was followed by exposure to methanesulfonic acid to afford dabrafenib mesylate (VI) in 85% yield.

Raf

Store at -20°C

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