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 complete conversion to the desired product. It was filtered when the mixture was still hot. The filtrate was cooled down to room temperature and the resulting precipitation was collected by filtration to afford 283a (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 down to room temperature
- customthe resulting precipitation
- filtrationwas collected by filtration
Sources & evidence
- ORD record
- ord-95de647408da4083a8c6c5fa2e2477f1
- Source dataset
- uspto-grants-2016_01
- Patent number
- US09238655B2
Reaction notes
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