Cesium carbonate → 5-chloro-N2-[5-(dimethylphosphoryl)-3-methoxypyrazin-2-yl]-N4-[2-(propan-2-ylsulfonyl)phenyl]pyrimidine-2,4-diamine

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	2,5-dichloro-N-(2-((1-methylethyl)sulfonyl)phenyl)-4-pyrimidinamine	HCID 59764378	—
Reactant	5-(Dimethylphosphoryl)-3-methoxypyrazin-2-amine	HCID 67052682	—
Catalyst	Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)	HCID 11029508	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	5-chloro-N2-[5-(dimethylphosphoryl)-3-methoxypyrazin-2-yl]-N4-[2-(propan-2-ylsulfonyl)phenyl]pyrimidine-2,4-diamine	HCID 68157112	6.4%

Reaction Conditions

Temperature	120 °C

Reaction Steps

To a mixture of 2,5-dichloro-N-[2-(propan-2-ylsulfonyl)phenyl]pyrimidin-4-amine (prepared in Example 32: 0.120 g, 0.348 mmol) and 5-(dimethylphosphoryl)-3-methoxypyrazin-2-amine (70.0 mg, 0.348 mmol) was added tris(dibenzylideneacetone)dipalladium(0)-chloroform adduct (17.6 mg, 0.017 mmol), XANTPHOS (23.3 mg, 0.040 mmol), and cesium carbonate (0.228 g, 0.700 mmol), and dioxane (3.5 mL). The mixture was sealed and heated at 120° C. After 16 h, the reaction mixture was cooled to rt and concentrated. The crude residue was purified by silica gel chromatography (0-10% 7N ammonia in methanol:dichloromethane) to afford the desired product (11.4 mg, 6% yield). MS/ES+: m/z=511.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09273077B2
Source dataset	uspto-grants-2016_03
ORD ID	ord-30ac62823c274683bc18ed3f4cf71172
Source note	uspto-grants-2016_03