Methyl iodide → N-butyl-2-(4-fluorophenyl)-3-[2-(methylsulfanyl)-4-pyrimidinyl]pyrazolo[1,5-a]pyridin-7-amine
Reaction equation
[CH2:1]([NH:5][C:6]1[N:11]2[N:12]=[C:13]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[C:14]([C:15]3[CH:20]=[CH:19][N:18]=[C:17]([S-:21])[N:16]=3)=[C:10]2[CH:9]=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH3:4].I[CH3:30].[OH-].[Na+]>O>[CH2:1]([NH:5][C:6]1[N:11]2[N:12]=[C:13]([C:22]3[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=3)[C:14]([C:15]3[CH:20]=[CH:19][N:18]=[C:17]([S:21][CH3:30])[N:16]=3)=[C:10]2[CH:9]=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH3:4]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
A mixture of 4-[7-(butylamino)-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-3-yl]-2-pyrimidinethiolate (2.87 g, 6.9 mmol) in 50 mL water was treated with iodomethane (0.86 mL, 13.8 mmol) and sodium hydroxide (4.1 mL, 5 N aqueous solution) and allowed to stir at room temperature for 4 hours. The mixture was diluted with additional water and extracted with dichloromethane. The organic layers were washed with brine, dried over magnesium sulfate and concentrated. Flash column chromatography eluting with 9:1 hexanes-ethyl acetate afforded N-butyl-2-(4-fluorophenyl)-3-[2-(methylsulfanyl)-4-pyrimidinyl]pyrazolo[1,5-α]pyridin-7-amine (1.64 g, 56%) as a yellow foam. 1H NMR (CDCl3): δ 8.15 (d, 1H), 7.73 (d, 1H), 7.56 (m, 2H), 7.33 (t, 1H), 7.13 (t, 2H), 6.62 (d, 1H), 6.02 (m, 2H), 3.35 (q, 2H), 2.55 (s, 3H), 1.76–1.41 (m, 4H), 0.95 (t, 3H); 19F NMR (CDCl3): δ −112.75; MS m/z 408 (M+1).
Workup
- extractionextracted with dichloromethane
- washThe organic layers were washed with brine
- dry with materialdried over magnesium sulfate
- concentrationconcentrated
- washFlash column chromatography eluting with 9:1 hexanes-ethyl acetate
Sources & evidence
- ORD record
- ord-5c3297f89954462188499559d81e2f28
- Source dataset
- uspto-grants-2007_01
- Patent number
- US07163940B2
Reaction notes
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