Cesium carbonate → 5-Bromo-1-methyl-3-(1-methyl-1H-imidazol-4-ylamino)pyridin-2(1H)-one

HRID 407709Notes

Reaction equation

[CH3:1][N:2]1[CH:6]=[C:5]([NH2:7])[N:4]=[CH:3]1.Br[C:9]1[C:10](=[O:17])[N:11]([CH3:16])[CH:12]=[C:13]([Br:15])[CH:14]=1.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.C(=O)([O-])[O-].[Cs+].[Cs+]>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].O1CCOCC1>[Br:15][C:13]1[CH:14]=[C:9]([NH:7][C:5]2[N:4]=[CH:3][N:2]([CH3:1])[CH:6]=2)[C:10](=[O:17])[N:11]([CH3:16])[CH:12]=1

Participants

Conditions

Temperature: 92 °C

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 1,4-dioxane (50 mL), 1-methyl-1H-imidazol-4-amine (1.1 g, 11.3 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (3.0 g, 11.3 mmol), Pd2(dba)3 (1.0 g, 1.13 mmol), XantPhos (1.3 g, 2.26 mmol), and cesium carbonate (7.3 g, 22.6 mmol). After three cycles of vacuum/argon flush, the mixture was heated at 92° C. for 4.5 hrs. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (100:1 to 50:1) to afford 130a (2.4 g, 76%) as a yellow solid. MS-ESI: [M+H]+ 283.1

Workup

customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
customAfter three cycles of vacuum/argon flush
temperatureIt was then cooled to room temperature
filtrationfiltered
concentrationThe filtrate was concentrated under reduced pressure
customthe resulting residue was purified by silica-gel column chromatography
washeluting with dichloromethane/methanol (100:1 to 50:1)

Sources & evidence

ORD record: ord-c3e176f2d2ec47e1a27f67a2ee6e6de8
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754077B2

Reaction notes

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