Potassium Phosphate, Tribasic → (4-(5-(5-(4-(2-Hydroxyethyl)piperazin-1-yl)pyridin-2-yl amino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-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-3-(5-(4-(2-hydroxyethyl)piperazin-1-yl)pyridin-2-ylamino)-1-methylpyridin-2(1H)-one	HCID 86684217	—
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-(5-(5-(4-(2-Hydroxyethyl)piperazin-1-yl)pyridin-2-yl amino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-3-yl)methyl acetate	HCID 86684218	—

Reaction Steps

A sealed tube was charged with 123c (200 mg, 0.49 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) (188 mg, 0.49 mmol), Pd(dppf)Cl2 (40 mg, 0.049 mmol), K3PO4 (208 mg, 0.98 mmol), NaOAc (133 mg, 0.98 mmol), H2O (3 mL), and MeCN (50 mL). The mixture was heated at 110° for 3 h. The solvent was evaporated in vacuo and the residue was purified by silica gel chromatography eluting with 30:1 DCM/MeOH to 123d (187 mg, 57%). MS: [M+H]+ 667.7.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09238655B2
Source dataset	uspto-grants-2016_01
ORD ID	ord-2fa3b137a256420f920a2866ff27fb98
Source note	uspto-grants-2016_01