Picolinic acid → 5-Chloro-3-(4-{[2-(trifluoromethyl)pyridin-4-yl]oxy}phenyl)-1,2-dihydropyridin-2-amine

Participants

Role	Name	HCID	Charge
Reactant	Picolinic acid	HCID 1018	—
Reactant	Potassium Phosphate, Tribasic	HCID 62657	—
Reactant	4-Bromo-2-(trifluoromethyl)pyridine	HCID 23436950	—
Reactant	4-(2-Amino-5-chloropyridin-3-yl)phenol	HCID 66748004	—
Catalyst	Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)	HCID 24350	—
Solvent	Dimethyl Sulfoxide	HCID 679	—
Product	5-Chloro-3-(4-{[2-(trifluoromethyl)pyridin-4-yl]oxy}phenyl)-1,2-dihydropyridin-2-amine	HCID 68280938	55.2%

Reaction Conditions

Temperature	140 °C

Reaction Steps

A mixture of 4-bromo-2-(trifluoromethyl)pyridine (282 mg), tripotassium phosphate (481 mg), picolinic acid (27.9 mg), copper(I) iodide (21.58 mg) and 4-(2-amino-5-chloropyridin-3-yl)phenol (250 mg) in DMSO (5 mL) was stirred at 140° C. under N2 overnight. The mixture was poured into sat.NH4Cl aq. and extracted with EtOAc. The organic layer was separated, washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography (NH silica gel, eluted with EtOAc in hexane) to give the title compound (230 mg) as a pale yellow solid.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08916551B2
Source dataset	uspto-grants-2014_12
ORD ID	ord-9d8779face264989ab6d2de92b6fbc61
Source note	uspto-grants-2014_12