Ethyl Acetoacetate → Ethyl 2-bromo-6-methyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylate
Reaction equation
[H-].[Na+].[C:3]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:4][C:5]([CH3:7])=O.Br[C:13]1[C:14]([NH2:20])=[N:15][CH:16]=[C:17]([Br:19])[N:18]=1>>[CH2:10]([O:9][C:3]([C:4]1[C:13]2[C:14](=[N:15][CH:16]=[C:17]([Br:19])[N:18]=2)[NH:20][C:5]=1[CH3:7])=[O:8])[CH3:11]Participants
Conditions
- Temperature
- 140 °C
Procedure
To a flask charged with 20 mL of anhydrous N-meythlpyrrolidine at 0° C. was added 60% NaH (840 mg, 21 mmol). After stirring 15 min, ethyl acetoacetate (2.73 g, 10.8 mmol) was added slowly. After stirring an additional 20 min 3,5-Dibromo-pyrazin-2-ylamine (5.04 g, 20 mmol). The reaction vessel was then removed from the ice bath and heated to 140° C. for 3 days. The dark mixture was cooled to rt and diluted with diethyl ether and water. The mixture was filtered and then partitioned. The organic layer was washed with water and then brine, dried over Na2SO4, filtered, and concentrated to afford a dark red oil. This was purified by silica gel chromatography (4:1 Hexanes:EtOAc) to afford 290 mg of 2-Bromo-6-methyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ethyl ester.
Workup
- additionTo a flask charged with 20 mL of anhydrous N-meythlpyrrolidine at 0° C.
- customThe reaction vessel was then removed from the ice bath
- temperatureThe dark mixture was cooled to rt
- additiondiluted with diethyl ether and water
- filtrationThe mixture was filtered
- custompartitioned
- washThe organic layer was washed with water
- dry with materialbrine, dried over Na2SO4
- filtrationfiltered
- concentrationconcentrated
- customto afford a dark red oil
- customThis was purified by silica gel chromatography (4:1 Hexanes:EtOAc)
Sources & evidence
- ORD record
- ord-223834535f6844cfa228af50edb33a0d
- Source dataset
- uspto-grants-2011_08
- Patent number
- US08008298B2
Reaction notes
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