CCT251545

Base Information

• Chemical Name: CCT251545
• CAS No.: 1661839-45-7
• Molecular Formula: C23H24ClN5O
• Molecular Weight: 421.92
• Mol file: 1661839-45-7.mol

Synonyms:CCT251545;8-[3-Chloro-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]-4-pyridinyl]-2,8-diazaspiro[4.5]decan-1-one;8-(3-chloro-5-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)pyridin-4-yl)-2,8-diazaspiro[4.5]decan-1-one

Chemical Property of CCT251545

Chemical Property:

• Boiling Point: 709.7±60.0 °C(Predicted)
• PKA: 15.81±0.20(Predicted)
• PSA: 117.31000
• Density: 1.37±0.1 g/cm3(Predicted)
• LogP: 7.91920
• Storage Temp.: Inert atmosphere,Store in freezer, under -20°C
• Solubility.: ≥42.2 mg/mL in DMSO; insoluble in H2O; ≥2.33 mg/mL in EtOH with ultrasonic

Purity/Quality:

99%+, ^*data from raw suppliers

CCT251545 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

• Description: CCT251545 is an orally bioavailable inhibitor of Wnt signaling (IC50 = 5 nM). It is a potent and selective inhibitor of the human mediator complex-associated protein kinases Cdk8 and Cdk19. Through its effects on Cdk8 and Cdk19, CCT251545 alters Wnt pathway-regulated gene expression. It reduces tumor growth in COLO 205 human colon cancer xenografts after oral dosing (70 mg/kg bid) and in Wnt-dependent tumors.
• Uses: CCT251545 is a potent inhibitor of WNT signaling with good oral pharmacokinetics.

Technology Process of CCT251545

There total 6 articles about CCT251545 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%

1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrazole (1607838-14-1) + 8-(3-bromo-5-chloropyridin-4-yl)-2,8-diazaspiro[4.5]decan-1-one → 8-{3-chloro-5-[4-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyridin-4-yl}-2,8-diazaspiro[4.5]decan-1-one (1661839-45-7)

Guidance literature:

With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; sodium carbonate; In water; acetonitrile; at 120 ℃; for 1h; Inert atmosphere;

Reference yield:

3-bromo-4,5-dichloro-pyridine (1001056-83-2) → 8-{3-chloro-5-[4-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyridin-4-yl}-2,8-diazaspiro[4.5]decan-1-one (1661839-45-7)

Guidance literature:

Multi-step reaction with 2 steps

1: triethylamine / 1 h / 220 °C / Microwave irradiation; Inert atmosphere

2: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; sodium carbonate / acetonitrile; water / 1 h / 120 °C / Inert atmosphere

With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; sodium carbonate; triethylamine; In water; acetonitrile; 2: |Suzuki Coupling;

Reference yield:

1-Chloro-4-iodobenzene (637-87-6) → 8-{3-chloro-5-[4-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyridin-4-yl}-2,8-diazaspiro[4.5]decan-1-one (1661839-45-7)

Guidance literature:

Multi-step reaction with 3 steps

1: sodium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / water; tetrahydrofuran / 80 °C

2: potassium acetate; XPhos; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ / 1,4-dioxane / 85 °C

3: sodium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / acetonitrile; water / 1 h / 120 °C / Microwave irradiation; Inert atmosphere

With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate; sodium carbonate; XPhos; In tetrahydrofuran; 1,4-dioxane; water; acetonitrile;

DOI:10.1021/jm501436m

upstream raw materials:

3-bromo-4,5-dichloro-pyridine

1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrazole

3-bromo-5-chloropyridine

1-Chloro-4-iodobenzene

Refernces

• 1、 Adeniji-Popoola, Olajumoke,Aherne, Wynne,Blagg, Julian,Box, Gary,Clarke, Paul A.,Court, William,Crumpler, Simon,Dale, Trevor,De Haven Brandon, Alexis,Eccles, Suzanne A.,Esdar, Christina,Georgi, Katrin,Henley, Alan T.,Hobbs, Steve,Leuthner, Birgitta,Mallinger, Aurlie,Ortiz-Ruiz, Maria-Jesus,Pichowicz, Mark,Poeschke, Oliver,Raynaud, Florence,Rohdich, Felix,Schiemann, Kai,Smith, Elizabeth,Stieber, Frank,Stubbs, Mark,Tepoele, Robert,Thai, Ching,Valenti, Melanie,Waalboer, Dennis,Wienke, Dirk,Wood, Bozena,Workman, Paul. "Discovery of potent, orally bioavailable, small-molecule inhibitors of WNT signaling from a cell-based pathway screen". . p. 1717 - 1735. Retrieved 2015/04/27.