Cesium carbonate → 4,4-Dimethyl-1-(5-trimethylsilanylethynyl-pyrimidin-2-yl)-pyrrolidin-2-one

Participants

Role	Name	HCID	Charge
Reactant	Cesium carbonate	HCID 10796	—
Reactant	4,4-Dimethyl-2-pyrrolidinone	HCID 637593	—
Reactant	2-Bromo-5-[(trimethylsilyl)ethynyl]pyrimidine	HCID 57516761	—
Catalyst	1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)	HCID 636044	—
Catalyst	Bis(dibenzylideneacetone)palladium	HCID 9811564	—
Solvent	Toluene	HCID 1140	—
Product	4,4-Dimethyl-1-(5-trimethylsilanylethynyl-pyrimidin-2-yl)-pyrrolidin-2-one	HCID 58464139	73.1%

Reaction Conditions

Temperature	90 °C

Reaction Steps

(200 mg, 0.78 mmol) 2-Bromo-5-trimethylsilanylethynyl-pyrimidine (Example 120, step 1) was dissolved in toluene (7 ml) and 4,4-dimethylpyrrolidin-2-one (89 mg, 0.78 mmol, 1.0 equiv.), cesium carbonate (410 mg, 1.25 mmol, 1.6 equiv.), xantphos (CAS 161265-03-8) (18 mg, 0.03 mmol, 0.04 equiv.) and Pd2(dba)3 (14 mg, 0.01 mmol, 0.02 equiv.) were added under nitrogen. The mixture was stirred for 2 hours at 90° C. The crude product was purified by flash chromatography by directly loading the toluene mixture onto a silica gel column and eluting with an ethyl acetate:heptane gradient 0:100 to 100:0. The desired 4,4-dimethyl-1-(5-trimethylsilanylethynyl-pyrimidin-2-yl)-pyrrolidin-2-one (164 mg, 73% yield) was obtained as a light red solid, MS: m/e=288.1 (M+H+).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09315498B2
Source dataset	uspto-grants-2016_04
ORD ID	ord-6b58108890f744898f6a3a5424156a92
Source note	uspto-grants-2016_04