Potassium Phosphate, Tribasic → 4-Fluoro-2-(5-(5-(3-(fluoromethyl)-4-methylpiperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-6-(1-oxo-3,4,6,7,8,9-hexa-hydropyrazino[1,2-a]indol-2(1H)-yl)benzyl acetate

Participants

Role	Name	HCID	Charge
Reactant	Potassium Phosphate, Tribasic	HCID 62657	—
Reactant	Sodium Acetate	HCID 517045	—
Reactant	5-Bromo-3-(5-(3-(fluoromethyl)-4-methylpiperazin-1-yl)pyridin-2-ylamino)-1-methylpyridin-2(1H)-one	HCID 58043731	—
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	—
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-(5-(5-(3-(fluoromethyl)-4-methylpiperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-6-(1-oxo-3,4,6,7,8,9-hexa-hydropyrazino[1,2-a]indol-2(1H)-yl)benzyl acetate	HCID 58044191	48.6%

Reaction Conditions

Temperature	110 °C

Reaction Steps

A mixture of 111g (1 g, 2.4 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 (1.3 g, 2.68 mmol), PdCl2(dppf) (190 mg, 0.24 mmol), K3PO4 (1 g, 4.8 mmol), and NaOAc (390 mg, 4.8 mmol) in MeCN (15 mL) and H2O (1.5 mL) was heated at 110° C. for 3 h. The solvent was evaporated in vacuo. The residue was purified on silica gel column (DCM: MeOH=50:1) to give 111h (0.8 g, yield 45%).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08729072B2
Source dataset	uspto-grants-2014_05
ORD ID	ord-6049040b47384218be76dededf819b05
Source note	uspto-grants-2014_05