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

HRID 407706Notes

Reaction equation

[CH3:1][C:2]1[O:6][N:5]=[C:4]([NH2:7])[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:4]2[CH:3]=[C:2]([CH3:1])[O:6][N:5]=2)[C:10](=[O:17])[N:11]([CH3:16])[CH:12]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 5-methylisoxazol-3-amine (1.0 g, 10.2 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (4.09 g, 15.3 mmol), Pd2(dba)3 (467 mg, 0.51 mmol), Xantphos (598 mg, 1.02 mmol), Cs2CO3 (6.65 g, 20.4 mmol), and dioxane (50 mL). After three cycles of vacuum/argon flush, the reaction mixture was heated at 100° C. for 3 h. Analysis of the reaction mixture by LCMS showed completed conversion to the desired product. It was filtered when the mixture was still hot. The filtrate was cooled to room temperature and the resulting precipitate was collected by filtration to afford 129a (1.6 g, 55%) as a yellow solid. MS-ESI: [M+H]+ 284.1

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
filtrationIt was filtered when the mixture
temperatureThe filtrate was cooled to room temperature
filtrationthe resulting precipitate was collected by filtration

Sources & evidence

ORD record: ord-f73f1153dc494d16be9da13cab7178ab
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754077B2

Reaction notes

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