Potassium Phosphate, Tribasic → [4-Fluoro-2-(1-methyl-5-{[5-(4-methylpiperazin-1-yl)pyridin-2-yl]amino}-6-oxo-1,6-dihydropyridin-3-yl)-6-{6-oxo-8-thia-5-azatricyclo[7.4.0.02,7]-trideca-1(9),2(7)-dien-5-yl}phenyl]methyl Acetate

https://huagongshe.com/reaction/1919004

Participants

Role	Name	HCID	Charge
Reactant	Potassium Phosphate, Tribasic	HCID 62657	—
Reactant	5-bromo-1-methyl-3-((5-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)pyridin-2(1H)-one	HCID 59216447	—
Reactant	2-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-4-fluoro-6-(1-oxo-3,4,5,6,7,8-hexahydrobenzothieno[2,3-c]pyridin-2(1H)-yl)benzyl Acetate	HCID 67016205	—
Reactant	HCID 178418247	HCID 178418247	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Water	HCID 962	—
Solvent	Acetonitrile	HCID 6342	—
Product	[4-Fluoro-2-(1-methyl-5-{[5-(4-methylpiperazin-1-yl)pyridin-2-yl]amino}-6-oxo-1,6-dihydropyridin-3-yl)-6-{6-oxo-8-thia-5-azatricyclo[7.4.0.02,7]-trideca-1(9),2(7)-dien-5-yl}phenyl]methyl Acetate	HCID 67016196	57.3%

Reaction Conditions

Temperature	110 °C

Reaction Steps

A 25 mL sealed tube was charged with 212b (990 mg, 2 mmol), 5-bromo-1-methyl-3-(5-(4-methylpiperazin-1-yl)pyridin-2-ylamino)pyridine-2(1H)-one 198e (500 mg, 1.3 mmol), CH3COONa (220 mg, 2.6 mmol), K3PO4 (700 mg, 2.6 mmol), and PdCl2(dppf) (110 mg, 0.13 mmol) suspended in CH3CN (25 mL) and water (1 mL). The mixture was heated at 110° C. for 2 hours. It was evaporated and the residue was purified by silical-gel column eluting with 20:1 methylene chloride/methanol to give 212c as a brown solid (500 mg, 56%). LCMS: [M+H]+ 670

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08618107B2
Source dataset	uspto-grants-2013_12
ORD ID	ord-1c47785217114cbb989d30007616e28c
Source note	uspto-grants-2013_12