Sodium Carbonate → {4-Fluoro-2-[1-methyl-5-({5-[4-methylpiperazin-1-yl]pyridin-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]-6-{7-oxo-3,6-diazatetracyclo[9.2.1.02,10.03,8]tetradeca-2(10),8-dien-6-yl}phenyl}methyl Acetate

https://huagongshe.com/reaction/1919165

Participants

Role	Name	HCID	Charge
Reactant	Sodium Carbonate	HCID 10340	—
Reactant	1-methyl-3-((5-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one	HCID 58043764	—
Reactant	(2-Bromo-4-fluoro-6-{7-oxo-3,6-diazatetracyclo[9.2.1.02,10.03,8]tetradeca-2(10),8-dien-6-yl}phenyl)methyl acetate	HCID 68096577	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	1,2-Dimethoxyethane	HCID 8071	—
Product	{4-Fluoro-2-[1-methyl-5-({5-[4-methylpiperazin-1-yl]pyridin-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]-6-{7-oxo-3,6-diazatetracyclo[9.2.1.02,10.03,8]tetradeca-2(10),8-dien-6-yl}phenyl}methyl Acetate	HCID 68096615	33%

Reaction Conditions

Temperature	130 °C

Reaction Steps

A microwave vial equipped with a magnetic stirrer was charged with (2-bromo-4-fluoro-6-{7-oxo-3,6-diazatetracyclo[9.2.1.02,10.03,8]tetradeca-2(10),8-dien-6-yl}phenyl)methyl acetate 334g (293 mg, 0.65 mmol), 1-methyl-5-(5-(4-methylpiperazin-1-yl)pyridine-2-ylamino)-6-oxo-1,6-dihydropyridin-3-ylboronic acid 197f (450 mg, 1.3 mmol), PdCl2(dppf) (54 mg, 0.065 mmol), 2.0 M Na2CO3 (2.0 equiv), and 1,2-dimethoxyethane (18 mL). After three cycles of vacuum/argon flash, the mixture was heated at 130° C. under microwave irradiation for 0.5 h. It was then filtered and the filtrate was evaporated in vacuo. The residue was purified on flash column chromatography eluting with 10:1 dichloromethane/methanol to afford 340a as a brown solid (130 mg, 33%). LCMS: [M+H]+ 666

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08618107B2
Source dataset	uspto-grants-2013_12
ORD ID	ord-6c4b9b0719cd4ee39c4cbf415332b65b
Source note	uspto-grants-2013_12