Tetrahydrofuran → HCID 86606804, compound
Reaction equation
[Cl:1][C:2]1[C:3]([N:8]2[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[N:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.C([NH:20][CH:21](C)C)(C)C.[Li].[Cl:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([CH3:32])[C:27]=1N=C=O.[O:36]1CCCC1>>[Cl:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([CH3:32])[C:27]=1[C:11]1[C:10]([C:13]([F:16])([F:14])[F:15])=[N:9][N:8]([C:3]2[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][N:4]=2)[C:12]=1[C:21]([NH2:20])=[O:36]Participants
Conditions
- Temperature
- 20 °C
Procedure
A solution of 3-chloro-2-[3-(trifluoromethyl)-1H-pyrazol-1-yl]pyridine (i.e. the pyrazole product from Step A) (2.72 g, 11.14 mmol) in tetrahydrofuran (50 ml) was cooled to −70° C. Lithium diisopropylamine (2M in THF/Heptane, 5.5 mL, 11.0 mmol) was added over 2 minutes and the mixture was stirred for 15 minutes. 2-Chloro-6-methylphenyl isocyanate (1.90 g, 11.33 mmol) was added via syringe. The mixture was allowed to warm to 20° C. and quenched with a saturated aqueous solution of ammonium chloride (50 mL). The reaction mass was extracted with ethyl acetate (100 mL), dried over magnesium sulfate and concentrated. Chromatography on silica gel with a gradient of 3:1 hexanes/ethyl acetate to 1:1 hexanes/ethyl acetate afforded the title compound, a compound of the present invention as a solid (3.0 g) melting at 212-213° C.
Workup
- customquenched with a saturated aqueous solution of ammonium chloride (50 mL)
- extractionThe reaction mass was extracted with ethyl acetate (100 mL)
- dry with materialdried over magnesium sulfate
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-c76fc6153a7a43ba81234df08c4efc68
- Source dataset
- uspto-grants-2010_07
- Patent number
- US07754738B2
Reaction notes
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