Sodium Carbonate → (R)-2-(5-(5-(2,4-Dimethylpiperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4-fluoro-6-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)benzyl acetate

Participants

Role	Name	HCID	Charge
Reactant	Sodium Carbonate	HCID 10340	—
Reactant	2-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-4-fluoro-6-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)benzyl Acetate	HCID 58044205	—
Reactant	(R)-5-Bromo-3-(5-(2,4-dimethylpiperazin-1-yl)pyridin-2-ylamino)-1-methylpyridin-2(1H)-one	HCID 86683720	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Dimethylformamide	HCID 6228	—
Solvent	Sodium chloride; water	HCID 57417360	—
Product	(R)-2-(5-(5-(2,4-Dimethylpiperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4-fluoro-6-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)benzyl acetate	HCID 86683721	53%

Reaction Conditions

Temperature	100 °C

Reaction Steps

A mixture of 109e (400 mg, 1.0 mmol), 4-fluoro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate (490 mg, 1.0 mmol), PdCl2(dppf) (80 mg, 0.1 mmol), 2.0 M Na2CO3 (2.0 equiv) in DMF (4 mL) was heated at 100° C. for 2 h. Brine was added and the mixture was extracted with EA (50 mL) three times. The combined organic layer was concentrated under reduced pressure. The residue was purified by flash column chromatography eluting with 30:1 DCM/MeOH to afford 109f as a brown solid (354 mg, 52%). LCMS: [M+H]+ 668

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08729072B2
Source dataset	uspto-grants-2014_05
ORD ID	ord-82eff69403dd4bbf951cff25e6861786
Source note	uspto-grants-2014_05