Cesium carbonate → N-(4-(4-amino-2,5-difluorophenoxy)pyridin-2-yl)cyclopropanecarboxamide

Participants

Role	Name	HCID	Charge
Reactant	Cesium carbonate	HCID 10796	—
Reactant	Cyclopropanecarboxamide	HCID 80376	—
Reactant	1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)	HCID 636044	—
Reactant	Benzenamine, 4-[(2-chloro-4-pyridinyl)oxy]-2,5-difluoro-	HCID 78358387	—
Catalyst	Bis(dibenzylideneacetone)palladium	HCID 9811564	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	N-(4-(4-amino-2,5-difluorophenoxy)pyridin-2-yl)cyclopropanecarboxamide	HCID 89588155	47%

Reaction Steps

A mixture of Example A2 (100 mg, 0.39 mmol), cyclopropanecarboxamide (100 mg, 1.17 mmol), Xantphos [4,5-bis(diphenylphosphino)-9,9-dimethylxanthene] (23 mg, 0.039 mmol), Cs2CO3 (254 mg, 0.78 mmol) and Pd2(dba)3 (22 mg, 0.023 mmol) in dioxane (10 mL) was heated at 100° C. for 2 hours. The mixture was cooled to RT and filtered to remove inorganic salts. The filtrate was concentrated under vacuum. The residue was diluted with water (100 mL) and extracted with EtOAc (3×100 mL). The combined organics were washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude product was purified by silica gel chromatography to afford N-(4-(4-amino-2,5-difluorophenoxy)pyridin-2-yl)cyclopropanecarboxamide (56 mg, 47% yield). MS (ESI): m/z 306.1 (M+H+).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09387202B2
Source dataset	uspto-grants-2016_07
ORD ID	ord-6e6c9b34fb3940989f0862a8941979f0
Source note	uspto-grants-2016_07