Futibatinib, also known as TAS-120 is an orally bioavailable inhibitor of the fibroblast growth factor receptor (FGFR) with potential antineoplastic activity. FGFR inhibitor TAS-120 selectively and irreversibly binds to and inhibits FGFR, which may result in the inhibition of both the FGFR-mediated signal transduction pathway and tumor cell proliferation, and increased cell death in FGFR-overexpressing tumor cells. FGFR is a receptor tyrosine kinase essential to tumor cell proliferation, differentiation and survival and its expression is upregulated in many tumor cell types.
This synthetic route was from WO2015008844
Step: 1.1 Reagents: Triethylamine
Catalysts: Cuprous iodide , Dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane addu…
Solvents: Dimethylformamide ; 6 h, 90 °C
Step 2.1 Reagents: Potassium carbonate
Solvents: Dimethylformamide ; 3 h, 70 °C
Step 3.1 Reagents: Hydrochloric acid
Solvents: 1,4-Dioxane ; 1.5 h, rt
Step 4.1 Reagents: Triethylamine
Solvents: Chloroform ; 0 °C; 10 min, rt
Step 4.2 Reagents: Sodium bicarbonate
Solvents: Water ; rt
Therapeutic agent containing 3,5-disubstituted benzene alkynyl compound for FGFR inhibitor-resistant cancer
By: Sootome, Hiroshi
World Intellectual Property Organization, WO2015008844 A1 2015-01-22
This synthetic route was from WO2013108809
Step 1.1 Reagents: Triethylamine
Catalysts: Cuprous iodide , Dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane addu…
Solvents: Dimethylformamide ; 6 h, 90 °C
Step 2.1 Reagents: Potassium carbonate
Solvents: Dimethylformamide ; 3 h, 70 °C
Step 3.1 Reagents: Hydrochloric acid
Solvents: 1,4-Dioxane ; 1.5 h, rt
Step 4.1 Reagents: Triethylamine
Solvents: Chloroform ; rt → 0 °C
Step 4.2 Solvents: Chloroform ; 10 min, rt
Step 4.3 Reagents: Sodium borohydride
Solvents: Water
Preparation of 3,5-disubstituted alkynylbenzene compounds as FGFR inhibitors
By: Sagara, Takeshi; et al
World Intellectual Property Organization, WO2013108809 A1 2013-07-25
