Foretinib (GSK1363089)

Base Information

• Chemical Name: Foretinib (GSK1363089)
• CAS No.: 849217-64-7
• Molecular Formula: C34H34F2N4O6
• Molecular Weight: 632.664
• Mol file: 849217-64-7.mol

Synonyms:N1'-[3-fluoro-4-[[6-methoxy-7-(3-morpholinopropoxy)-4-quinolyl]oxy]phenyl]-N1-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide;N-[3-Fluoro-4-[[6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-quinolinyl]oxy]phenyl]-N'-(4-fluorophenyl)-1,1-cyclopropanedicarboxamide; N-[3-Fluoro-4-[[6-(methyloxy)-7-[[3-(morpholin-4-yl)propyl]oxy]quinolin-4-yl]oxy]phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide;GSK 1363089;

Chemical Property of Foretinib (GSK1363089)

Chemical Property:

• Boiling Point: 828.475 °C at 760 mmHg
• PKA: 13.14±0.70(Predicted)
• Flash Point: 454.846 °C
• PSA: 116.45000
• Density: 1.373 g/cm³
• LogP: 5.98340
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• Solubility.: DMSO (Slightly), Ethanol (Slightly)

Purity/Quality:

99% ^*data from raw suppliers

Foretinib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: Foretinib (GSK1363089) is an ATP-competitive inhibitor of HGFR and VEGFR, mostly for Met and KDR with IC50 of 0.4 nM and 0.9 nM in cell-free assays. Less potent against Ron, Flt-1/3/4, Kit, PDGFRα/β and Tie-2, and little activity to FGFR1 and EGFR. Phase 2. Foretinib is a multikinase inhibitor that targets MET and VEGFR2 and also exhibits an inhibitory effect against KIT, Flt-3, PDGFRb, and Tie-2.
• Uses: Foretinib (GSK1363089) is an ATP-competitive inhibitor of hepatocyte growth factor (HGF) and Vascular endothelial growth factor (VEGF) Receptor Tyrosine Kinases.
• Clinical Use: Foretinib has also shown to be effective against ROS1 mutations especially when acquired with crizotinib resistance. A clinical trial investigating the dosing and safety profile of combining foretinib and erlotinib was designed for advanced pretreated NSCLC patients.

Technology Process of Foretinib (GSK1363089)

There total 35 articles about Foretinib (GSK1363089) 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: 89.0%

3-Fluoro-4-{[6-methoxy-7-(3-morpholinopropoxy)-4-quinolyl]oxy}-aniline (479690-10-3) + ((4-fluorophenyl)carbamoyl)cyclopropanecarboxylic acid (849217-48-7) → foretinib (849217-64-7)

Guidance literature:

((4-fluorophenyl)carbamoyl)cyclopropanecarboxylic acid; With oxalyl dichloride; N,N-dimethyl-formamide; In tetrahydrofuran; at 15 - 20 ℃; Industry scale;

3-Fluoro-4-{[6-methoxy-7-(3-morpholinopropoxy)-4-quinolyl]oxy}-aniline; With potassium carbonate; In tetrahydrofuran; at 15 - 20 ℃; for 3h; Industry scale;

Reference yield: 83.0%

4-chloro-6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinoline (205448-32-4) + N'-(3-fluoro-4-hydroxyphenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (849217-58-9) → foretinib (849217-64-7)

Guidance literature:

With potassium phosphate; racemic-2-(di-tert-butylphosphino)-1,1′-binaphthyl; palladium diacetate; In 1-methyl-pyrrolidin-2-one; toluene; at 95 ℃; for 2h; Product distribution / selectivity; Inert atmosphere;

Reference yield: 72.0%

N-[3-fluoro-4-[[7-hydroxy-6-methoxy-quinolin-4-yl]oxy]phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (849217-50-1) + N-(3-chloropropyl)morpholine hydrochloride (57616-74-7) → foretinib (849217-64-7)

Guidance literature:

With potassium carbonate; In N,N-dimethyl-formamide; at 90 ℃; for 5h;

upstream raw materials:

N-[3-fluoro-4-[[7-hydroxy-6-methoxy-quinolin-4-yl]oxy]phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

N-(3-chloropropyl)morpholine hydrochloride

4-chloro-6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinoline

N'-(3-fluoro-4-hydroxyphenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Refernces

• 1、 -. "A tyrosine kinase inhibitor and intermediate preparation method". . . Retrieved 2017/10/13.
• 2、 -. "CRYSTALLINE FORMS OF N-[3-FLUORO-4-({6-(METHYLOXY)-7-[(3-MORPHOLIN-4-YLPROPYL)OXY]-QUIN0LIN-4-YL}OXY)PHENYL]-N'-(4-FLUOROPHENYL)CYCLOPROPANE-1, 1-DICARBOXAMIDE". Page/Page column 18-20. . Retrieved 2011/02/24.