Cesium carbonate → N-(4-chloro-3,5-difluorophenyl)-3-nitropyridin-2-amine
Reaction equation
[Cl:1][C:2]1[C:8]([F:9])=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[F:10].Cl[C:12]1[C:17]([N+:18]([O-:20])=[O:19])=[CH:16][CH:15]=[CH:14][N:13]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.O>[Cl:1][C:2]1[C:8]([F:9])=[CH:7][C:5]([NH:6][C:12]2[C:17]([N+:18]([O-:20])=[O:19])=[CH:16][CH:15]=[CH:14][N:13]=2)=[CH:4][C:3]=1[F:10]Participants
Conditions
- Temperature
- 80 °C
Procedure
A mixture of 4-chloro-3,5-difluoroaniline (1.64 g, 10.0 mmol), 2-chloro-3-nitropyridine (1.56 g, 9.84 mmol) and cesium carbonate (6.56 g, 20.1 mmol) in N,N-dimethylformamide (30 mL) was stirred at 80° C. for 36 hours. The reaction mixture was cooled to room temperature, diluted with water (200 mL) and extracted with ethyl acetate (3×200 mL). The combined organic layers were washed with saturated aqueous sodium chloride solution (5×50 mL), dried over sodium sulfate, filtered, concentrated in vacuo and purified by chromatography on silica gel (Gradient: 0% to 5% ethyl acetate in petroleum ether) to provide the product as a yellow solid. Yield: 200 mg, 0.70 mmol, 7%. 1H NMR (400 MHz, CDCl3) δ 10.23 (br s, 1H), 8.55-8.61 (m, 2H), 7.52 (br d, J=9 Hz, 2H), 6.96-7.01 (m, 1H).
Workup
- temperatureThe reaction mixture was cooled to room temperature
- extractionextracted with ethyl acetate (3×200 mL)
- washThe combined organic layers were washed with saturated aqueous sodium chloride solution (5×50 mL)
- dry with materialdried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
- custompurified by chromatography on silica gel (Gradient: 0% to 5% ethyl acetate in petroleum ether)
Sources & evidence
- ORD record
- ord-838a493be2ad4f70a0e55835e1efd114
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09120788B2
Reaction notes
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