LY2801653

Base Information

• Chemical Name: LY2801653
• CAS No.: 1206799-15-6
• Molecular Formula: C30H22F2N6O3
• Molecular Weight: 552.54
• Mol file: 1206799-15-6.mol

Synonyms:LY2801653;N-(3-fluoro-4-((1-Methyl-6-(1H-pyrazol-4-yl)-1H-indazol-5-yl)oxy)phenyl)-1-(4-fluorophenyl)-6-Methyl-2-oxo-1,2-dihydropyridine-3-carboxaMide;N-[3-Fluoro-4-[[1-methyl-6-(1H-pyrazol-4-yl)-1H-indazol-5-yl]oxy]phenyl]-1-(4-fluorophenyl)-1,2-dihydro-6-methyl-2-oxo-3-pyridinecarboxamide

Chemical Property of LY2801653

Chemical Property:

• Boiling Point: 795.3±60.0 °C(Predicted)
• PKA: 10.83±0.70(Predicted)
• PSA: 106.83000
• Density: 1.42±0.1 g/cm3(Predicted)
• LogP: 5.81850
• Solubility.: ≥27.65 mg/mL in DMSO; insoluble in H2O; ≥5.02 mg/mL in EtOH with gentle warming and ultrasonic

Purity/Quality:

97% ^*data from raw suppliers

N-(3-Fluoro-4-((1-methyl-6-(1H-pyrazol-4-yl)-1H-indazol-5-yl)oxy)phenyl)-1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide 95% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: MET is a tyrosine kinase that leads to downstream activation of several pathways including RAS and MAPK.?As a result, it is quite possible that MET inhibition can be active in RAS mutant tumors and maybe associated with EGFR resistance in NSCLC.?Two MET inhibitors, tivantinib and onartuzumab, have been examined in KRAS mutant NSCLC with others in clinical trials at this time. LY2801653 is an orally bioavailable MET kinase inhibitor (Ki = 2 nM). It also inhibits MST1R, Axl, MNK1/2, FLT3, DDR1, and DDR2 (IC50s = 11, 2, 7, 7, 0.1, and 7 nM, respectively, in a cell-based assay). It inhibits MET autophosphorylation stimulated by hepatocyte growth factor (HGF) in H460 and S114 cells (IC50s = 35.2 and 59.2 nM, respectively) and inhibits growth of Ba/F3 cells transfected with MET-activating mutations (IC50s = 12-248 nM). LY2801653 (0.01-10 μM) completely blocks cell scattering induced by HGF in DU145 cells. It reduces tumor growth in MET autocrine (U-87MG) and MET over-expression (H441) mouse xenograft models when administered at doses of 4 and 12 mg/kg.
• Clinical Use: Preclinical testing also has shown merestinib to inhibit several other receptor tyrosine oncokinases including MST1R, FLT3, AXL, MERTK, TEK, ROS1, and NTRK1/2/3.

Technology Process of LY2801653

There total 29 articles about LY2801653 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: 99.5%

tert-butyl 4-(5-(2-fluoro-4-(1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamido)phenoxy)-1-methyl-1H-indazol-6-yl)-1H-pyrazole-1-carboxylate (1206801-36-6) → N-(3-fluoro-4-((1-methyl-6-(1H-pyrazol-4-yl)-1H-indazol-5-yl)oxy)phenyl)-1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide (1206799-15-6)

Guidance literature:

With 1,8-diazabicyclo[5.4.0]undec-7-ene; In ethanol; for 9h; Reagent/catalyst; Solvent; Temperature; Reflux; Large scale;

DOI:10.1021/op400317z

Reference yield: 94.0%

N-(4-((6-(1-(1-ethoxyethyl)-1H-pyrazol-4-yl)-1-methyl-1H-indazol-5-yl)oxy)-3-fluorophenyl)-1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide → N-(3-fluoro-4-((1-methyl-6-(1H-pyrazol-4-yl)-1H-indazol-5-yl)oxy)phenyl)-1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide (1206799-15-6)

Guidance literature:

With water; ammonium chloride; In tetrahydrofuran; at 150 ℃; for 2h; under 12929 Torr; Reagent/catalyst; Temperature; Pressure; Autoclave; Large scale;

DOI:10.1021/acs.oprd.5b00240

Reference yield:

N-(3-fluoro-4-(1-methyl-6-(1H-pyrazol-4-yl)-1H-indazol-5-yloxy)phenyl)-1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide hydrochloride (1206801-37-7) → N-(3-fluoro-4-((1-methyl-6-(1H-pyrazol-4-yl)-1H-indazol-5-yl)oxy)phenyl)-1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide (1206799-15-6)

Guidance literature:

With sodium carbonate; In dichloromethane; water; at 20 ℃; for 0.5h; pH=9.4;

upstream raw materials:

tert-butyl 4-(5-(2-fluoro-4-(1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamido)phenoxy)-1-methyl-1H-indazol-6-yl)-1H-pyrazole-1-carboxylate

N-(3-fluoro-4-(1-methyl-6-(1H-pyrazol-4-yl)-1H-indazol-5-yloxy)phenyl)-1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide hydrochloride

tert-butyl 4-(5-(2-fluoro-4-nitrophenoxy)-1-methyl-1H-indazol-6-yl)-1H-pyrazole-1-carboxylate

tert-butyl 4-(5-(4-amino-2-fluorophenoxy)-1-methyl-1H-indazol-6-yl)-1H-pyrazole-1-carboxylate