Cesium carbonate → 1-{4-(3-Chloro-4-fluoro-phenyl)-6-[4-(3-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyrimidin-2-yl}-4-propyl-piperazin-2-one

Participants

Role	Name	HCID	Charge
Reactant	Cesium carbonate	HCID 10796	—
Reactant	1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)	HCID 636044	—
Reactant	Tert-butyl 3-oxopiperazine-1-carboxylate	HCID 3157178	—
Reactant	2-Chloro-4-(3-chloro-4-fluoro-phenyl)-6-[4-(3-trifluoromethylpyridin-2-yl)-piperazin-1-yl]-pyrimidine	HCID 57761490	—
Catalyst	Bis(dibenzylideneacetone)palladium	HCID 9811564	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	1-{4-(3-Chloro-4-fluoro-phenyl)-6-[4-(3-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyrimidin-2-yl}-4-propyl-piperazin-2-one	HCID 57761639	—

Reaction Conditions

Temperature	90 °C

Reaction Steps

To a solution of 2-chloro-4-(3-chloro-4-fluoro-phenyl)-6-[4-(3-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyrimidine (259 mg, 0.55 mmol), 3-oxo-piperazine-1-carboxylic acid tert-butyl ester (prepared essentially as described by Kane and Carr (1980) Teit. Lett. 21:3019-20; 132 mg, 0.66 mmol) and Cs2CO3 (250 mg, 0.77 mmol) in dioxane, add 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (19 mg, 0.03 mmol). Purge the reaction mixture for 10 minutes with nitrogen gas and then add Pd2(dba)3 (10 mg, 0.011 mmol). After purging with nitrogen gas for an additional 5 minutes, heat the mixture at 90° C. for 16 hours under nitrogen atmosphere. Filter the mixture through celite and concentrate under reduced pressure to give the title compound.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07566712B2
Source dataset	uspto-grants-2009_07
ORD ID	ord-a19edf61d7dc49f98e32f7742fc042b7
Source note	uspto-grants-2009_07