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

HRID 629234Notes

Reaction equation

CS([C:5]1[N:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:7][N:6]=1)(=O)=O.[CH3:19][C:20]1([CH3:26])[CH2:24][NH:23][C:22](=[O:25])[CH2:21]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1>[CH3:19][C:20]1([CH3:26])[CH2:24][N:23]([C:5]2[N:10]=[CH:9][C:8]([C:11]#[C:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[CH:7][N:6]=2)[C:22](=[O:25])[CH2:21]1

Participants

Conditions

Temperature: 100 °C

Procedure

(100 mg, 0.39 mmol) 2-Methanesulfonyl-5-phenylethynyl-pyrimidine (Example 115, step 1) was dissolved in 1 ml dioxane. 4,4-Dimethylpyrrolidin-2-one (53 mg, 465 μmol, 1.2 equiv.) and cesium carbonate (190 mg, 580 μmol, 1.5 equiv.) were added at room temperature. The mixture was stirred for 4 hours at 100° C. The reaction mixture was cooled, evaporated and extracted with saturated NaHCO3 solution and two times with a small volume of dichloromethane. The crude product was purified by flash chromatography by directly loading the dichloromethane layers 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-phenylethynyl-pyrimidin-2-yl)-pyrrolidin-2-one (32 mg, 28% yield) was obtained as a light yellow solid, MS: m/e=292.1 (M+H+).

Workup

temperatureThe reaction mixture was cooled
customevaporated
extractionextracted with saturated NaHCO3 solution and two times with a small volume of dichloromethane
customThe crude product was purified by flash chromatography
washeluting with an ethyl acetate

Sources & evidence

ORD record: ord-b8fc3c4b0fc2458a99ec77a7a256029c
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09315498B2

Reaction notes

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