Potassium Phosphate, Tribasic → N-[(1S)-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]oxy]-1-methyl-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	(S)-N-(1-(6-(5-bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-ylamino)pyridin-2-yloxy)propan-2-yl)acrylamide	HCID 118116485	—
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-[(1S)-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]oxy]-1-methyl-ethyl]prop-2-enamide	HCID 118117062	27.1%

Reaction Conditions

Temperature	85 °C

Reaction Steps

A mixture of (S)—N-(1-(6-(5-bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-ylamino)pyridin-2-yloxy)propan-2-yl)acrylamide 107d (150 mg, 0.37 mmol), 108c (200 mg, 0.40 mmol), Pd(dppf)Cl2(27 mg, 10 mol %) and K3PO4(235 mg, 1.11 mmol) in acetonitrile (20 mL) and water (5 ml) was stirred at 85° C. for 4 h under nitrogen. The reaction mixture was cooled to rt and concentrated. The residue was purified by prep-TLC (DCM/MeOH=30/1) to give 108d (70 mg crude) as yellow solid

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09260415B2
Source dataset	uspto-grants-2016_02
ORD ID	ord-ff7455d3665d4a0c8766c1c596c6eb23
Source note	uspto-grants-2016_02