PLX3397 (Pexidartinib)

Base Information

• Chemical Name: PLX3397 (Pexidartinib)
• CAS No.: 1029044-16-3
• Molecular Formula: C20H15ClF3N5
• Molecular Weight: 417.821
• Mol file: 1029044-16-3.mol

Synonyms:PLX3397 (Pexidartinib);PLX-3397;Pexidartinib (PLX3397);Pexidartinib;3-Pyridinemethanamine,N-[5-[(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl]-2-pyridinyl]-6-(trifluoromethyl)-;N-[5-[(5-Chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl]-2-pyridinyl]-6-(trifluoromethyl)-3-pyridinemethanamine

Chemical Property of PLX3397 (Pexidartinib)

Chemical Property:

• PKA: 12.81±0.40(Predicted)
• PSA: 66.49000
• Density: 1.458±0.06 g/cm3(Predicted)
• LogP: 5.30100
• Storage Temp.: -20°C
• Solubility.: Soluble in DMSO (up to at least 10 mg/ml)

Purity/Quality:

99% ^*data from raw suppliers

Pexidartinib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: Pexidartinib (TURALIO?) is a novel, orally available small molecule tyrosine kinase inhibitor (TKI) with potent and selective activity against the colony-stimulating factor 1 (CSF1) receptor. Pexidartinib also inhibits KIT proto-oncogene receptor tyrosine kinase (KIT) and FMS-like tyrosine kinase 3 harboring an internal tandem duplication mutation (FLT3-ITD). Pexidartinib has been developed by Daiichi Sankyo for the treatment of tenosynovial giant cell tumor (TGCT; also known as giant cell tumor of the tendon sheath or pigmented villonodular synovitis. Colony stimulating factor 1 (CSF1) is a cytokine that is involved in the recruitment and activation of tissue macrophages. It exerts these effects by binding to its corresponding receptor tyrosine kinase, the cFMS/CSF1 receptor (CSF1R). Pexidartinib is a brain-penetrant inhibitor of CSF1R, as well as c-Kit and FLT3 (IC50s = 20, 10, and 160 nM in vitro, respectively). It has been used in combination with paclitaxel to block macrophage recruitment in mammary tumor-bearing mice, thus slowing primary tumor development and metastasis. Pexidartinib has also been used to block microglial stimulation of glioblastoma invasion in both cell culture and a mouse model of glioblastoma multiforme.
• Uses: Pexidartinib is RTK inhibitor. It can be used in pharmacological activity, therapeutic use, and biological study of inhibition of colony stimulating factor-1 receptor improves antitumor efficacy of BRAF inhibition.

Technology Process of PLX3397 (Pexidartinib)

There total 28 articles about PLX3397 (Pexidartinib) which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 98.1%

C20H15ClF3N5O3 → 5-((5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl)-N-((6-(trifluoromethyl)pyridin-3-yl)methyl)pyridin-2-amine (1029044-16-3)

Guidance literature:

With 5%-palladium/activated carbon; hydrogen; ammonium chloride; In methanol; at 30 - 35 ℃; for 6h; under 1500.15 - 2250.23 Torr; Solvent; Reagent/catalyst; Temperature; Autoclave; Green chemistry;

Reference yield: 92.0%

tert-butyl 3-((6-((tert-butoxycarbonyl)((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)pyridin-3-yl)methyl)-5-chloro-1H-pyrrolo[2,3-b]pyridine-1-carboxylate → 5-((5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl)-N-((6-(trifluoromethyl)pyridin-3-yl)methyl)pyridin-2-amine (1029044-16-3)

Guidance literature:

With trifluoroacetic acid; In dichloromethane; at 20 ℃;

DOI:10.1021/jacs.1c05092

Reference yield: 89.4%

5-[(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl]pyridin-2-amine + 6-(trifluoromethyl)pyridine-3-carbaldehyde (386704-12-7,872626-76-1) → 5-((5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl)-N-((6-(trifluoromethyl)pyridin-3-yl)methyl)pyridin-2-amine (1029044-16-3)

Guidance literature:

With triethylsilane; trifluoroacetic acid; In acetonitrile; at 15 - 82 ℃;

upstream raw materials:

tert-butyl N-[(tert-butoxy)carbonyl]-N-(5-formylpyridin-2-yl)carbamate

5-chloro-1H-pyrrolo[2,3-b]pyridine

C₂₃H₂₇ClN₄O₅

6-(trifluoromethyl)pyridine-3-carbaldehyde

Refernces

• 1、 Cao, Yuhui,Che, Jinteng,Chen, Han,Chen, Si-Cong,Fang, Xianhe,Guo, Yinliang,Guo, Zhixian,Kong, Lingran,Li, Chen,Lu, Jia-Tian,Luo, Tuoping,Zhang, Nan,Zhu, Qi. "Dealkenylative Ni-Catalyzed Cross-Coupling Enabled by Tetrazine and Photoexcitation". . p. 14046 - 14052. Retrieved 2021/09/13.
• 2、 -. "Synthetic method for continuously producing pexidartinib". Paragraph 0040-0044; 0047-0052; 0055-0060; 0063. . Retrieved 2020/06/20.