Sodium Iodide → 3-ethyl-6-methyl-5-pyrazol-1-yl-1H-pyridin-2-one
Reaction equation
[CH2:1]([C:3]1[C:4]([O:15]C)=[N:5][C:6]([CH3:14])=[C:7]([N:9]2[CH:13]=[CH:12][CH:11]=[N:10]2)[CH:8]=1)[CH3:2].[I-].[Na+].C(#N)C.Cl[Si](C)(C)C>O>[CH2:1]([C:3]1[C:4](=[O:15])[NH:5][C:6]([CH3:14])=[C:7]([N:9]2[CH:13]=[CH:12][CH:11]=[N:10]2)[CH:8]=1)[CH3:2]Participants
Conditions
- Temperature
- 65 °C
Procedure
To a mixture of 3-ethyl-2-methoxy-6-methyl-5-pyrazol-1-yl-pyridine (98 mg, 0.452 mmol) and sodium iodide (203 mg, 1.35 mmol) under a N2 atmosphere is added anhydrous acetonitrile (3 mL) followed by dropwise addition of chlorotrimethylsilane (170 μL, 1.35 mmol). The reaction mixture is stirred at 65° C. under nitrogen for 13 h. The reaction mixture is allowed to cool, diluted with water and the resulting mixture is extracted with 3 portions of dichloromethane. The combined extracts are dried over magnesium sulfate and evaporated to leave an orange residue. The crude product is triturated with ether/heptane to give 3-ethyl-6-methyl-5-pyrazol-1-yl-1H-pyridin-2-one as a light orange solid (75 mg, 82% yield). This material (30 mg) is dissolved in dichloromethane (2 mL) and treated with ethereal hydrochloric acid (2.0 M, 0.444 mL). The mixture is stirred for 1.5 h, evaporated and triturated with ether to give 3-ethyl-6-methyl-5-pyrazol-1-yl-1H-pyridin-2-one hydrochloride (29 mg) as a white powder. LC/MS: RT: 2.15 min, MS: m/e=204 (M+H); 1H NMR (CDCl3, δ ppm): 7.73 (1H, d), 7.55 (1H, d), 7.47 (1H, s), 6.47 (1H, t), 2.62 (2H, q), 2.33 (3H, s), 1.22 (3H, t).
Workup
- temperatureto cool
- extractionthe resulting mixture is extracted with 3 portions of dichloromethane
- dry with materialThe combined extracts are dried over magnesium sulfate
- customevaporated
- customto leave an orange residue
- customThe crude product is triturated with ether/heptane
Sources & evidence
- ORD record
- ord-eb6e73bb2ff74548b57664ec7711591b
- Source dataset
- uspto-grants-2012_05
- Patent number
- US08173682B2
Reaction notes
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