Potassium Phosphate, Tribasic → N-[2-[[6-[[5-[5-fluoro-2-(acetoxymethyl)-3-(4-oxo-6,7,8,9-tetrahydrobenzothiopheno[2,3-d]pyridazin-3-yl)phenyl]-1-methyl-2-oxo-3-pyridyl]amino]-2-pyridyl]amino]ethyl]prop-2-enamide

Participants

Role	Name	HCID	Charge
Reactant	Potassium Phosphate, Tribasic	HCID 62657	—
Reactant	(4-Fluoro-2-{6-oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-trien-5-yl}-6-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methyl acetate	HCID 58043634	—
Reactant	N-(2-(6-(5-bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-ylamino)pyridin-2-ylamino)ethyl)acrylamide	HCID 118116339	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Water	HCID 962	—
Solvent	Acetonitrile	HCID 6342	—
Product	N-[2-[[6-[[5-[5-fluoro-2-(acetoxymethyl)-3-(4-oxo-6,7,8,9-tetrahydrobenzothiopheno[2,3-d]pyridazin-3-yl)phenyl]-1-methyl-2-oxo-3-pyridyl]amino]-2-pyridyl]amino]ethyl]prop-2-enamide	HCID 118116546	31%

Reaction Conditions

Temperature	85 °C

Reaction Steps

A mixture of 105e (235 mg, 0.601 mmol), (4-fluoro-2-{6-oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-triene-5-yl}-6-(tetra-methyl-1,3,2-dioxaborolan-2-yl)phenyl)methyl acetate 108c (299 mg, 0.601 mmol), Pd(dppf)Cl2(42.8 mg, 0.06 mmol) and K3PO4(382 mg, 1.80 mmol) in ACN (10 mL) and H2O (2 mL) was degassed and stirred at 85° C. for 4 h under nitrogen. The reaction mixture was concentrated and the residue was purified by silica gel chromatography (EA/PE=4/1) to give N-[2-[[6-[[5-[5-fluoro-2-(acetoxymethyl)-3-(4-oxo-6,7,8,9-tetrahydrobenzothiopheno[2,3-d]pyridazin-3-yl)phenyl]-1-methyl-2-oxo-3-pyridyl]amino]-2-pyridyl]amino]ethyl]prop-2-enamide 105f (125 mg, 31%) as a brown solid. MS-ESI: [M+H]+ 684.3

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09260415B2
Source dataset	uspto-grants-2016_02
ORD ID	ord-97c8daf41aa143ceb6eb6a5fafa89d2a
Source note	uspto-grants-2016_02