TIANFU CHEM N-[3-[5-(2-Amino-4-pyrimidinyl)-2-(tert-butyl)-4-thiazolyl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide

Details:

Product Name: N-[3-[5-(2-Amino-4-pyrimidinyl)-2-(tert-butyl)-4-thiazolyl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide
Synonyms: Dabrafenib;N-[3-[5-(2-Amino-4-pyrimidinyl)-2-(tert-butyl)-4-thiazolyl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide;Dabrafenib free base(GSK2118436A);Dabrafenib (GSK2118436);GSK2118436A;Dabrafenib (GSK2118436A);Dabrafenib KB-57246;Debrafenib API
CAS: 1195765-45-7
MF: C23H20F3N5O2S2
MW: 519.5624096
EINECS:
Product Categories: Raf B protein kinase inhibitor;inhibitor;MAPK;Inhibitors
Mol File: 1195765-45-7.mol
N-[3-[5-(2-Amino-4-pyrimidinyl)-2-(tert-butyl)-4-thiazolyl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide Structure
N-[3-[5-(2-Amino-4-pyrimidinyl)-2-(tert-butyl)-4-thiazolyl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide Chemical Properties
density  1.443

Overview Dabrafenib(trade name Tafinlar, GSK2118436) is a type of targeted therapy known as a signal transduction inhibitor that helps slow or stop the growth and spread of melanoma cells in the form of methanesulfonate for medicinal purposes.
Trametinib was previously approved in 2013 as a single agent for treatment of BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma. Dabrafenib was also approved in 2013 as a single agent for treatment of BRAF V600E mutation-positive unresectable or metastatic melanoma. Trametinib and dabrafenib target two different kinases in the RAS/RAF/MEK/ERK pathway. The combination of these two drugs is considered to be able to produce more effective and lasting therapeutical effect of melanoma, and the composition of two drugs are also considered to be major business opportunities of two drugs.
The patients who have advanced stages of melanoma will benifit from this drug:
Stage III that is unresectable (unable to be completely removed by surgery)
Stage IV, also known as metastatic (melanoma cells that have spread to organs and other parts of the body).
If you have advanced melanoma, your physician will test you for BRAF mutations before prescribing dabrafenib. The physician will send a biopsy (sample of cancer tissue removed from your body) to a special lab for analysis. Dabrafenib:
When given by itself, works only in patients who have tested positive for the BRAF V600E mutation.
Cannot be used to treat patients with the wild-type BRAF mutation.
Synthetic Methods The key step in the synthesis of Dabrafenib is the construction of the 1,3-thiazole ring, which is usually carried out by the closing ring directly of thioamide (as a 1,3-binuclear reagent) and anα-carbonyl halide (as a 1,2-amphiphilic reagent). Sulfonyl chloride 1 and aniline 2 gave sulfonamide 3 under basic conditions. Methyl pyrimidine 4 with non-nucleophilic strong alkali LiHMDS pull out the acid proton on the methyl and react with 3 to obtain 5, and the latter has α-bromination with NBS to obtain 1,2-amphiphilic reagent 6, and then 6 reacts with 1 , 3-parent nucleotides 7 to close the ring to obtain 8, and finally reacts with ammonia to obtain Dabrafenib.