Dabrafenib Mesylate Chemical Properties

Melting point:

>234oC (dec.)

storage temp. 

Hygroscopic, -20°C Freezer, Under inert atmosphere

solubility 

DMSO (Slightly, Heated), Methanol (Slightly)

form 

White solid.

color 

White to Off-White

Stability:

Hygroscopic

InChI

InChI=1S/C23H20F3N5O2S2.CH4O3S/c1-23(2,3)21-30-18(19(34-21)16-10-11-28-22(27)29-16)12-6-4-9-15(17(12)26)31-35(32,33)20-13(24)7-5-8-14(20)25;1-5(2,3)4/h4-11,31H,1-3H3,(H2,27,28,29);1H3,(H,2,3,4)

InChIKey

YKGMKSIHIVVYKY-UHFFFAOYSA-N

SMILES

S(O)(=O)(=O)C.FC1C(=CC=CC=1C1N=C(C(C)(C)C)SC=1C1C=CN=C(N)N=1)NS(C1C(=CC=CC=1F)F)(=O)=O

Safety Information

HS Code 

2935909099

Dabrafenib Mesylate Usage And Synthesis

Description

Dabrafenib Mesylate(1195768-06-9) is a salt form of Dabrafenib. Dabrafenib is an inhibitor of certain mutated forms of BRAF kinase, several of which may be associated with stimulating tumour growth (e.g. the BRAF V600E mutation), and Dabrafenib is also an inhibitor of BRAF V600-mutation positive cancer cell growth, both in vitro and in vivo.

Description

Dabrafenib mesylate, sold by GlaxoSmithKline under the trade name Tafinlar, was approved by the U.S. FDA in May 2013 for the treatment of metastatic BRAF-mutant melanoma. Dabrafenib reversibly inhibits the BRAF(V600E) mutant kinase as a selective ATP-competitive inhibitor which results in tumor regression.

Uses

Dabrafenib is an inhibitor of mutated BRAF kinase and has clinical activity with a manageable safety profile in clinical trials of phase 1 and 2 in patients with BRAF(V600)-mutated metastatic melanoma.

Definition

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

Synthesis

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.

target

Raf

storage

Store at -20°C

References

[1]namba h, nakashima m, hayashi t, hayashida n, maeda s, rogounovitch ti, ohtsuru a, saenko va, kanematsu t, yamashita s. clinical implication of hot spot braf mutation, v599e, in papillary thyroid cancers. j. clin. endocrinol. metab. 2003; 88 (9): 4393–7.
[2]tan yh, liu y, eu kw, ang pw, li wq, salto-tellez m, iacopetta b, soong r. detection of braf v600e mutation by pyrosequencing. pathology 2008; 40 (3): 295–8.
[3]davies h, bignell gr, cox c, et al. mutations of the braf gene in human cancer. nature. 2002; 417: 949-954.
[4]ma xh, piao sf, dey s, mcafee q, karakousis g, villanueva j, hart ls, levi s, hu j, zhang g, lazova r, klump v, pawelek jm, xu x, xu w, schuchter lm, davies ma, herlyn m, winkler j, koumenis c, amaravadi rk. targeting er stress-induced autophagy overcomes braf inhibitor resistance in melanoma. j clin invest. 2014; 124(3): 1406-17.

Dabrafenib Mesylate(1195768-06-9)Related Product Information

• Methanesulfonic acid
• Phentolamine mesilate
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• Crizotinib
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• Vandetanib