GSK-2126458

Base Information

• Chemical Name: GSK-2126458
• CAS No.: 1086062-66-9
• Molecular Formula: C25H17F2N5O3S
• Molecular Weight: 505.504
• Hs Code.: 29350090
• Mol file: 1086062-66-9.mol

Synonyms:GSK 2126458;2,4-Difluoro-N-[2-methoxy-5-[4-(4-pyridazinyl)-6-quinolinyl]-3-pyridinyl]benzenesulfonamide;

Chemical Property of GSK-2126458

Chemical Property:

• Melting Point: 187-189 °C
• Boiling Point: 715.6±70.0 °C(Predicted)
• PKA: 6.23±0.40(Predicted)
• PSA: 115.34000
• Density: 1.45 g/cm³
• LogP: 5.99520
• Storage Temp.: Refrigerator
• Solubility.: Chloroform (Slightly), DMSO (Slightly), Methanol (Very Slightly, Heated)

Purity/Quality:

98%,99%, ^*data from raw suppliers

GSK2126458 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: GSK2126458 is a potent inhibitor of phosphoinositide 3-kinase isoforms (Kis = 19, 130, 24, and 60 pM for p110α, β, δ, and γ, respectively). It also inhibits mTOR in both mTORC1 and mTORC2 (Kis = 180 and 300 nM, respectively), as well as several common mutant forms of p110α. GSK2126458 is orally bioavailable, displays favorable pharmacokinetics, and shows efficacy in tumor growth models. GSK2126458 positively combines with inhibitors of discoidin domain receptor 1 (DDR1) inhibitor DDR1-IN-1 to suppress the growth of SNU-1040 colorectal cancer cells.
• Uses: A highly potent inhibitor of PI3K and the mammalian target of Rapamycin.

Technology Process of GSK-2126458

There total 12 articles about GSK-2126458 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: 76.0%

N-(5-bromo-2-methoxypyridine-3-yl)-2,4-difluorobenzene sulfonyl chloride (1086063-46-8) + 6-bromo-4-(pyridazin-4-yl)quinoline (1086063-18-4) → GS(264)K2158 (1086062-66-9)

Guidance literature:

With potassium acetate; bis(pinacol)diborane; In 1,4-dioxane; at 100 ℃; for 3h;

Reference yield:

5-bromo-2-chloro-3-nitropyridine (67443-38-3) → GS(264)K2158 (1086062-66-9)

Guidance literature:

Multi-step reaction with 4 steps

1: methanol / 0 - 20 °C

2: tin(II) chloride dihdyrate / ethyl acetate / 4 h / Reflux

3: pyridine / 0 - 20 °C

4: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; sodium carbonate / 1,4-dioxane / Reflux

With pyridine; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; tin(II) chloride dihdyrate; sodium carbonate; In 1,4-dioxane; methanol; ethyl acetate;

DOI:10.1016/j.bmcl.2011.12.136

Reference yield:

N-(5-bromo-2-methoxypyridine-3-yl)-2,4-difluorobenzene sulfonyl chloride (1086063-46-8) + C19H20BN3O2 → GS(264)K2158 (1086062-66-9)

Guidance literature:

With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; sodium carbonate; In 1,4-dioxane; Reflux;

DOI:10.1016/j.bmcl.2011.12.136

upstream raw materials:

6-bromo-4-chloroquinoline

6-bromo-4-iodoquinoline

6-bromo-4-chloroquinoline hydrochloride

5-bromo-2-(methyloxy)-3-pyridinamine

Downstream raw materials:

2,4-difluoro-N-(2-hydroxy-5-(4-(pyridazin-4-yl)quinolin-6-yl)pyridin-3-yl)benzenesulfonamide

Refernces

• 1、 Wang, Min,Gao, Mingzhang,Miller, Kathy D.,Sledge, George W.,Zheng, Qi-Huang. "[11C]GSK2126458 and [18F]GSK2126458, the first radiosynthesis of new potential PET agents for imaging of PI3K and mTOR in cancers". . p. 1569 - 1574. Retrieved 2012/04/04.