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

HRID 629236Notes

Reaction equation

Br[C:2]1[N:7]=[CH:6][C:5]([C:8]#[C:9][Si:10]([CH3:13])([CH3:12])[CH3:11])=[CH:4][N:3]=1.[CH3:14][C:15]1([CH3:21])[CH2:19][NH:18][C:17](=[O:20])[CH2:16]1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[CH3:14][C:15]1([CH3:21])[CH2:19][N:18]([C:2]2[N:7]=[CH:6][C:5]([C:8]#[C:9][Si:10]([CH3:13])([CH3:12])[CH3:11])=[CH:4][N:3]=2)[C:17](=[O:20])[CH2:16]1

Participants

Conditions

Temperature: 90 °C

Procedure

(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+).

Workup

customThe crude product was purified by flash chromatography
washeluting with an ethyl acetate

Sources & evidence

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

Reaction notes

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