Water → 3-Chloro-5-[methyl(1-methylpropyl)amino]pyrazine-2-carbaldehyde
Reaction equation
P(Cl)(Cl)(Cl)=O.[Cl:6][C:7]1[N:12]=[C:11]([N:13]([CH3:18])[CH:14]([CH3:17])[CH2:15][CH3:16])[CH:10]=[N:9][CH:8]=1.O.CN([CH:23]=[O:24])C>>[Cl:6][C:7]1[C:8]([CH:23]=[O:24])=[N:9][CH:10]=[C:11]([N:13]([CH3:18])[CH:14]([CH3:17])[CH2:15][CH3:16])[N:12]=1Participants
Procedure
Phosphoryl chloride (1.33 mL) was added dropwise to DMF (5 mL) at 0° C. The mixture was stirred for 15 min, and a solution of 6-chloro-N-methyl-N-(1-methylpropyl)pyrazin-2-amine (1.43 g) in DMF (1 mL) was added dropwise thereto. The mixture was stirred at 80° C. for 18 hr, water (5 mL) was added at 0° C., and the mixture was stirred at room temperature for 1.5 hr. The mixture was extracted with ethyl acetate. The aqueous layer was extracted again with ethyl acetate. The combined organic layer was washed with water and saturated brine, dried over magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (solvent gradient: 10'50% ethyl acetate/hexane) to give the title compound (1.43 g, 88%) as a pale-yellow oil.
Workup
- stirringThe mixture was stirred at 80° C. for 18 hr
- stirringthe mixture was stirred at room temperature for 1.5 hr
- extractionThe mixture was extracted with ethyl acetate
- extractionThe aqueous layer was extracted again with ethyl acetate
- washThe combined organic layer was washed with water and saturated brine
- dry with materialdried over magnesium sulfate
- concentrationconcentrated
- customThe residue was purified by silica gel column chromatography (solvent gradient
Sources & evidence
- ORD record
- ord-a3699e8e0bfd44cc9e21e29f46309695
- Source dataset
- uspto-grants-2012_11
- Patent number
- US08314088B2
Reaction notes
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