Reaction equation
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([S:9][CH3:10])[N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:17][C:18]1[N:22]=[C:21]([CH3:23])[NH:20][N:19]=1>CN(C=O)C>[Cl:8][C:6]1[CH:7]=[C:2]([N:19]2[C:18]([CH3:17])=[N:22][C:21]([CH3:23])=[N:20]2)[N:3]=[C:4]([S:9][CH3:10])[N:5]=1Participants
Procedure
To a slurry of 4,6-dichloro-2-(methylthio)pyrimidine (1-1) (1.00 g, 5.13 mmol, 1.0 eq.) and cesium carbonate (2.70 g, 7.67 mmol, 1.5 eq.) in DMF (40 mL) at 0° C. under nitrogen was added a solution of 3,5-dimethyl-1H-1,2,4-triazole (498 mg, 5.13 mmol, 1.0 eq.) in DMF (20 mL) via a dropping funnel over 1 hour. The reaction was then warmed to room temperature. The reaction was monitored by TLC and was complete after 1 hour. The reaction was quenched by addition of water (100 mL) and extracted with ethyl acetate (3×150 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated to dryness. The resulting residue was purified by silica gel column chromatography (0-50% ethyl acetate in hexanes) to afford 4-chloro-6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-(methylthio)pyrimidine (1-2) as a white solid. 1H NMR (300 MHz, CDCl3) δ 7.58 (s, 1H), 2.90 (s, 3H), 2.60 (s, 3H), 2.41 (s, 3H). LRMS m/z (M+H) 256 found, 256 required.
Workup
- customThe reaction was quenched by addition of water (100 mL)
- extractionextracted with ethyl acetate (3×150 mL)
- dry with materialThe combined organic layers were dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated to dryness
- customThe resulting residue was purified by silica gel column chromatography (0-50% ethyl acetate in hexanes)
Sources & evidence
- ORD record
- ord-e213b06102f5448daba1e33d562d7afb
- Source dataset
- uspto-grants-2015_12
- Patent number
- US09200001B2
Linked notes
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