Cesium carbonate → [5-(3-Amino-3-methyl-but-1-ynyl)-2-methoxy-phenyl]-[6-(2,4-difluoro-phenylamino)-pyridin-3-yl]-methanone

Participants

Role	Name	HCID	Charge
Reactant	Cesium carbonate	HCID 10796	—
Reactant	3-Butyn-2-amine, 2-methyl-	HCID 76319	—
Reactant	(5-Bromo-2-methoxy-phenyl)-[6-(2,4-difluoro-phenylamino)-pyridin-3-yl]-methanone	HCID 22349594	—
Catalyst	Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)	HCID 24350	—
Catalyst	HCID 178418476	HCID 178418476	—
Solvent	Diisopropylethylamine	HCID 81531	—
Product	[5-(3-Amino-3-methyl-but-1-ynyl)-2-methoxy-phenyl]-[6-(2,4-difluoro-phenylamino)-pyridin-3-yl]-methanone	HCID 10180494	—

Reaction Steps

(5-Bromo-2-methoxy-phenyl)-[6-(2,4-difluoro-phenylamino)-pyridin-3-yl]-methanone (1.36 g; 3.2 mmol) is dissolved in hot diisopropylethylamine (120 ml). PdCl2(PPh3)2 (680 mg; 0.97 mmol), Cs2CO3 (6.8 g; 0.02 mmol), CuI (0.68 g; 3.57 mmol) and 1,1-dimethyl-prop-2-ynylamine (6.8 ml; 65 mmol) are added and the mixture refluxed under argon for 30 min. The reaction mixture is decanted from the solid, evaporated, taken up in water and extracted three times with ethyl acetate. The combined organic phases are dried over Na2SO4 and evaporated to dryness. Purification via chromatography (SiO2; toluene/ethanol/NH3conc 96/4/0.2>94/6/0.3) yields the title compound as a slightly colored foam (1.14 g; 84%).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US06919336B2
Source dataset	uspto-grants-2005_07
ORD ID	ord-aa4313d367454407a66153bd4db34413
Source note	uspto-grants-2005_07