Cesium carbonate → 4-chloro-6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidine
Reaction equation
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([CH3:9])[N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:16][C:17]1[N:21]=[C:20]([CH3:22])[NH:19][N:18]=1>CN(C=O)C>[Cl:8][C:6]1[CH:7]=[C:2]([N:18]2[C:17]([CH3:16])=[N:21][C:20]([CH3:22])=[N:19]2)[N:3]=[C:4]([CH3:9])[N:5]=1Participants
Procedure
To a slurry of 4,6-dichloro-2-methylpyrimidine (1-1) (5.00 g, 30.7 mmol) and cesium carbonate (15.0 g, 46 mmol) in DMF (250 mL) at 0° C. was added a solution of 3,5-dimethyl-1H-1,2,4-triazole (2.98 g, 30.7 mmol) in DMF (50 mL) via a dropping funnel over 1 h. The reaction was then warmed to room temperature and stirred for 1 h. The reaction was quenched by addition of water (500 mL) and extracted with ethyl acetate (3×400 mL). The combined organic layer was dried over sodium sulfate, filtered and concentrated. The crude product was purified by silica gel column chromatography (0-30% EtOAc/hexanes) to afford 4-chloro-6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidine (1-2) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.75 (s, 1H), 2.91 (s, 3H), 2.72 (s, 3H), 2.41 (s, 3H); MS m/z=224 (M+H).
Workup
- customThe reaction was quenched by addition of water (500 mL)
- extractionextracted with ethyl acetate (3×400 mL)
- dry with materialThe combined organic layer was dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
- customThe crude product was purified by silica gel column chromatography (0-30% EtOAc/hexanes)
Sources & evidence
- ORD record
- ord-6bf8e6b5d0a84ce4a982c052430be053
- Source dataset
- uspto-grants-2016_06
- Patent number
- US09359348B2
Reaction notes
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