Potassium Phosphate, Tribasic → 2-(10-Fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-4-(1-methyl-5-(2-methylpyrimidin-4-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde

Participants

Role	Name	HCID	Charge
Reactant	Potassium Phosphate, Tribasic	HCID 62657	—
Reactant	Sodium Acetate	HCID 517045	—
Reactant	1-Methyl-3-(2-methylpyrimidin-4-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one	HCID 86683935	—
Reactant	4-Chloro-2-(10-fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)nicotinaldehyde	HCID 86684238	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Water	HCID 962	—
Solvent	Acetonitrile	HCID 6342	—
Product	2-(10-Fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-4-(1-methyl-5-(2-methylpyrimidin-4-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde	HCID 86684395	57.3%

Reaction Conditions

Temperature	100 °C

Reaction Steps

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 4-chloro-2-(10-fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)nicotinaldehyde 134c (150 mg, 0.43 mmol), 213b (147 mg 0.43 mmol), Pd(dppf)Cl2 (35 mg, 0.043 mmol), sodium acetate (71 mg, 0.86 mmol), K3PO4 (182 mg, 0.86 mmol), water (0.5 mL), and acetonitrile (15 mL). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. for 2.5 h. After cooling to room temperature the reaction was filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica-gel column chromatography eluting with 40:1 dichloromethane/methanol to afford 213c as a yellow solid (130 mg, 57%). MS-ESI: [M+H]+ 528.2.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09238655B2
Source dataset	uspto-grants-2016_01
ORD ID	ord-ae5fb517704b4e4c967953e79b1b4124
Source note	uspto-grants-2016_01