Cesium carbonate → 5-Bromo-1-methyl-3-(5-methylisoxazol-3-ylamino)pyridin-2(1H)-one
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]=1Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
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-5758c9c0c80e4f72b8e416082c355994
- Source dataset
- uspto-grants-2014_03
- Patent number
- US08669251B2
Reaction notes
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