Carbon Disulfide → 6-fluoro-2H-imidazo[1,5-a]pyridine-3-thione
Reaction equation
Cl.Cl.[F:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:10][NH2:11])=[N:8][CH:9]=1.C(N(CC)CC)C.[C:19](=S)=[S:20]>CO>[F:3][C:4]1[CH:5]=[CH:6][C:7]2[N:8]([C:19](=[S:20])[NH:11][CH:10]=2)[CH:9]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 75 °C
Procedure
In a round-bottomed flask, (5-fluoropyridin-2-yl)methylamine dihydrochloride (600 mg, 3.0 mmol) was suspended in methanol (16 ml). Triethylamine (1.4 ml, 10.0 mmol) was added followed by carbon disulfide (1.4 ml, 23.2 mmol). The reaction mixture was stirred at reflux (oil bath temperature=75° C.) overnight then cooled to room temperature and then concentrated. The residue was partitioned between dichloromethane and water. The aqueous layer was extracted with dichloromethane then the organic layers were combined, dried over sodium sulfate, filtered and concentrated. The residue was absorbed on silica gel and chromatographed with EtOAc/hexanes (gradient 0-60% EtOAc) to afford 169 mg (33%) of 6-fluoro-2H-imidazo[1,5-a]pyridine-3-thione as an orange solid. 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 13.47 (br. s., 1H), 8.04 (dd, J=4.9, 1.1 Hz, 1H), 7.43-7.56 (m, 2H), 6.88 (ddd, J=10.0, 7.9, 2.1 Hz, 1H).
Workup
- temperaturethen cooled to room temperature
- concentrationconcentrated
- customThe residue was partitioned between dichloromethane and water
- extractionThe aqueous layer was extracted with dichloromethane
- dry with materialdried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
- customThe residue was absorbed on silica gel
- customchromatographed with EtOAc/hexanes (gradient 0-60% EtOAc)
Sources & evidence
- ORD record
- ord-ec1fc6a5f33148e2bd8328892b52fa07
- Source dataset
- uspto-grants-2014_02
- Patent number
- US08658646B2
Reaction notes
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