Cesium carbonate → 3-{2-[2-((R)-1-Hydroxyethyl)benzoimidazol-1-yl]-9-methyl-6-morpholin-4-yl-9H-purin-8-ylmethylene}azetidine-1-carboxylic acid tert-butyl ester

https://huagongshe.com/reaction/1945684

Participants

Role	Name	HCID	Charge
Reactant	Cesium carbonate	HCID 10796	—
Reactant	(1R)-1-(1H-1,3-benzodiazol-2-yl)ethan-1-ol	HCID 729393	—
Reactant	2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl	HCID 11155794	—
Reactant	tert-butyl 3-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methylene)azetidine-1-carboxylate	HCID 59605709	—
Catalyst	Tris(dibenzylideneacetone) dipalladium	HCID 9832798	—
Solvent	Toluene	HCID 1140	—
Product	3-{2-[2-((R)-1-Hydroxyethyl)benzoimidazol-1-yl]-9-methyl-6-morpholin-4-yl-9H-purin-8-ylmethylene}azetidine-1-carboxylic acid tert-butyl ester	HCID 59605933	72%

Reaction Conditions

Temperature	140 °C

Reaction Steps

A mixture of 3-(2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-ylmethylene)azetidine-1-carboxylic acid tert-butyl ester (180 mg, 0.43 mmol), (R)-1-(1H-benzoimidazol-2-yl)ethanol (84 mg, 0.52 mmol), tris(dibenzylideneacetone) dipalladium (40 mg, 0.04 mmol), XPhos (82 mg, 0.17 mmol) and Cs2CO3 (279 mg, 0.86 mmol) in toluene (3 mL) was purged with argon then heated at 140° C. for 1 h in a microwave reactor. The reaction mixture was filtered through Celite®, washing with EtOAc and the filtrate concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-15%) affording the title compound (167 mg, 72%). LCMS (method A): RT 3.24 min [M+H]+ 547.4

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08394796B2
Source dataset	uspto-grants-2013_03
ORD ID	ord-e3798c0c2f2a4ffd90c409e58899439f
Source note	uspto-grants-2013_03