S)-1-(sec-butyl)-N-((4,6-diMethyl-2-oxo-1,2-dihydropyridin-3-yl)Methyl)-3-Methyl-6-(6-(piperazin-1-yl)pyridin-3-yl)-1H-indole-4-carboxaMide

Base Information

• Chemical Name: S)-1-(sec-butyl)-N-((4,6-diMethyl-2-oxo-1,2-dihydropyridin-3-yl)Methyl)-3-Methyl-6-(6-(piperazin-1-yl)pyridin-3-yl)-1H-indole-4-carboxaMide
• CAS No.: 1346574-57-9
• Molecular Formula: C31H38N6O2
• Molecular Weight: 526.67
• Hs Code.: 2933998090
• Mol file: 1346574-57-9.mol

Synonyms:N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-((1S)-1-methylpropyl)-6-[6-(1-;GSK126 - inhibitor of histone methyltransferase EZH2;

Chemical Property of S)-1-(sec-butyl)-N-((4,6-diMethyl-2-oxo-1,2-dihydropyridin-3-yl)Methyl)-3-Methyl-6-(6-(piperazin-1-yl)pyridin-3-yl)-1H-indole-4-carboxaMide

Chemical Property:

• Boiling Point: 823.4±65.0 °C(Predicted)
• PKA: 11.93±0.10(Predicted)
• PSA: 98.80000
• Density: 1.25±0.1 g/cm3(Predicted)
• LogP: 6.00830
• Storage Temp.: -20°C Freezer
• Solubility.: DMSO (Slightly), Methanol (Slightly, Heated)

Purity/Quality:

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

GSK126 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

• Description: The histone H3 lysine 27 (H3K27) methyltransferase EZH2 plays an important role in regulating gene expression, and its aberrant activity is linked to the onset and progression of cancer. GSK126 is a selective, S-adenosyl-methionine-competitive small molecule inhibitor of EZH2 methyltransferase activity (Ki = 0.57 nM; IC50 = 9.9 nM versus that of EZH1: Ki = 89 nM; IC50 = 680 nM). It is more than 1,000-fold selective for EZH2 over other histone methyltranferases, including both SET-domain-containing and non-SET-domain-containing methyltransferases. At concentrations of 7-252 nM, it has been shown to inhibit global H3K27 trimethylation levels and to reactivate silenced PRC2 target genes. Furthermore, GSK126 can inhibit the proliferation of EZH2 mutant DLBCL cell lines (IC50 = 28-61 nM) as well as the growth of EZH2 mutant DLBCL xenografts in mice receiving a daily dose of 50 mg/kg.
• Uses: GSK126 is a potent and highly selective S-adenosyl-methionine-competitive small molecule inhibitor of EZH2 methyltransferase enzyme activity. The inhibition activity of GSK126 on EZH2 activity may pro vide a promising treatment for EZH2 mutant lymphoma. GSK126 is a potent and highly selective S-adenosyl-methionine-competitive small molecule inhibitor of EZH2 methyltransferase enzyme activity. The inhibition activity of GSK126 on EZH2 activity may provide a promising treatment for EZH2 mutant lymphoma.

Technology Process of S)-1-(sec-butyl)-N-((4,6-diMethyl-2-oxo-1,2-dihydropyridin-3-yl)Methyl)-3-Methyl-6-(6-(piperazin-1-yl)pyridin-3-yl)-1H-indole-4-carboxaMide

There total 19 articles about S)-1-(sec-butyl)-N-((4,6-diMethyl-2-oxo-1,2-dihydropyridin-3-yl)Methyl)-3-Methyl-6-(6-(piperazin-1-yl)pyridin-3-yl)-1H-indole-4-carboxaMide 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: 92.0%

1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazine (871125-86-9) + (S)-6-bromo-1-(sec-butyl)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-methyl-1H-indole-4-carboxamide (1346574-54-6) → GSK-126 (1346574-57-9)

Guidance literature:

With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; In water; at 90 ℃; Reagent/catalyst; Inert atmosphere;

Reference yield:

6-bromo-1-(sec-butyl)-3-methyl-1H-indole-4-carboxylic acid (1346575-54-9) → GSK-126 (1346574-57-9)

Guidance literature:

Multi-step reaction with 3 steps

1: 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 4-methyl-morpholine / dimethyl sulfoxide / 32 h / 20 °C / Inert atmosphere; Sealed tube

2: isopropylamine / n-heptane; ethanol / 20 °C / Resolution of racemate

3: sodium carbonate / dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / 1,2-dimethoxyethane; water / 0.17 h / 140 °C / Inert atmosphere; Microwave irradiation; Sealed vial

With 4-methyl-morpholine; 1-hydroxy-7-aza-benzotriazole; sodium carbonate; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; isopropylamine; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; In 1,2-dimethoxyethane; ethanol; n-heptane; water; dimethyl sulfoxide; 3: Suzuki Coupling;

Reference yield:

6-bromo-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylpropyl)-1H-indole-4-carboxamide (1346574-53-5) → GSK-126 (1346574-57-9)

Guidance literature:

Multi-step reaction with 2 steps

1: isopropylamine / n-heptane; ethanol / 20 °C / Resolution of racemate

2: sodium carbonate / dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / 1,2-dimethoxyethane; water / 0.17 h / 140 °C / Inert atmosphere; Microwave irradiation; Sealed vial

With sodium carbonate; isopropylamine; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; In 1,2-dimethoxyethane; ethanol; n-heptane; water; 2: Suzuki Coupling;

upstream raw materials:

1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazine

(S)-6-bromo-1-(sec-butyl)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-methyl-1H-indole-4-carboxamide

6-bromo-1-(sec-butyl)-3-methyl-1H-indole-4-carboxylic acid

6-bromo-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylpropyl)-1H-indole-4-carboxamide

Refernces

• 1、 Lu, Chen,Zhang, Qiang,Chen, Xin. "New method for synthesis of EZH2 methyltransferase inhibitor GSK126". supporting information. p. 1215 - 1222. Retrieved 2016/08/05.
• 2、 -. "INDOLES". Page/Page column 83-84. . Retrieved 2011/11/30.