tert-Butyl piperazine-1-carboxylate → 1-Boc-4-(3-amino-6-bromopyrazin-2-YL)piperazine
Reaction equation
[NH2:1][C:2]1[C:7](Br)=[N:6][C:5]([Br:9])=[CH:4][N:3]=1.[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11]>CCOC(C)=O>[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][N:20]([C:7]2[C:2]([NH2:1])=[N:3][CH:4]=[C:5]([Br:9])[N:6]=2)[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:11])[CH3:12]Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 120 °C
Procedure
2-Amino-3,5-dibromopyrazine (1.26 g, 5.0 mmol) and piperazine-1-carboxylic acid tert-butyl ester (4.64 g, 25 mmol) were placed in a dry RBF and heated with stirring to 120° C. under dry nitrogen. Molten mixture was stirred at this temperature for 6 h and cooled to room temperature. The resulting slurry was diluted with EtOAc (20 mL) and stirred for 20 min. Amine salts were removed by filtration and washed with EtOAc (3×5 mL). Filtrate was washed with pH 4 buffer (35 mL) and brine (35 mL), dried over Na2SO4 (anhydrous), filtered, and concentrated in vacuo. The residue was purified by flash chromatography (hexanes/EtOAc 7:3) gives the title compound I-3r as an off white solid (1.64 g, 92% yield).
Workup
- temperatureheated
- stirringMolten mixture was stirred at this temperature for 6 h
- temperaturecooled to room temperature
- stirringstirred for 20 min
- customAmine salts were removed by filtration
- washwashed with EtOAc (3×5 mL)
- washFiltrate was washed with pH 4 buffer (35 mL) and brine (35 mL)
- dry with materialdried over Na2SO4 (anhydrous)
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe residue was purified by flash chromatography (hexanes/EtOAc 7:3)
Sources & evidence
- ORD record
- ord-d70f6060e70648bca8937a602e994a9d
- Source dataset
- uspto-grants-2005_05
- Patent number
- US06894050B2
Reaction notes
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