Potassium Phosphate, Tribasic → (4-(1-Methyl-5-(5-(methylsulfonyl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridine-3-yl)methyl acetate

Participants

Role	Name	HCID	Charge
Reactant	Potassium Phosphate, Tribasic	HCID 62657	—
Reactant	Sodium Acetate	HCID 517045	—
Reactant	(2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methyl acetate	HCID 86684143	—
Reactant	5-Bromo-1-methyl-3-(5-(methylsulfonyl)pyridin-2-ylamino)pyridin-2(1H)-one	HCID 86684203	—
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-(1-Methyl-5-(5-(methylsulfonyl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridine-3-yl)methyl acetate	HCID 86684204	57.9%

Reaction Conditions

Temperature	100 °C

Reaction Steps

A sealed tube was charged with 117d (100 mg, 0.28 mmol), 3-(acetoxymethyl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-4-ylboronic acid 113i (115 mg, 0.3 mmol), PdCl2(dppf) (25 mg, 0.03 mmol), K3PO4 (126 mg, 0.6 mmol), and NaOAc (60 mg, 0.6 mmol) in MeCN (8 mL) and H2O (1 mL). The system was evacuated and refilled with N2. The reaction mixture was heated at 100° C. for 2 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel flash column eluting with DCM:MeOH (20:1) to afford 117e (100 mg, 40%). MS: [M+H]+ 617.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08716274B2
Source dataset	uspto-grants-2014_05
ORD ID	ord-169d1e981a194086b274e731f815f278
Source note	uspto-grants-2014_05