Hydrochloric Acid → 3-Amino-6-(2,6-difluorophenyl)-2-pyrazinecarboxylic acid
Reaction equation
[NH2:1][C:2]1[C:3]([C:16]([O:18]C)=[O:17])=[N:4][C:5]([C:8]2[C:13]([F:14])=[CH:12][CH:11]=[CH:10][C:9]=2[F:15])=[CH:6][N:7]=1.O.[OH-].[Li+].Cl>C1COCC1.O>[NH2:1][C:2]1[C:3]([C:16]([OH:18])=[O:17])=[N:4][C:5]([C:8]2[C:13]([F:14])=[CH:12][CH:11]=[CH:10][C:9]=2[F:15])=[CH:6][N:7]=1Participants
Procedure
A solution of methyl 3-amino-6-(2,6-difluorophenyl)pyrazine-2-carboxylate (258 mg, 0.973 mmol) and lithium hydroxide monohydrate (200 mg, 4.8 mmol) in THF (4.0 mL) and water (2.0 mL) was heated at 60° C. in a sealed vial for 2 h. The reaction mixture was allowed to cool to ambient temperature and neutralized by the addition of 1.0 M hydrogen chloride in water (4.8 mL, 4.8 mmol) to form a precipitate. The precipitate was collected by filtration, washed with EtOAc (5 mL), and dried under vacuum to afford the sub-title compound (170 mg). The filtrate was diluted with EtOAc (15 mL) and the layers were separated. The organic layer was washed with H2O (3 mL) and the combined aqueous phases were extracted with EtOAc (3 mL). The combined organic layers were washed with brine (3 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to provide additional sub-title compound. The crude product was used in the subsequent reaction without further purification (70 mg). LC/MS (ESI) calc. for C11H8F2N3O2(M+H)+: m/z=252.1. found: 251.9.
Workup
- customto form a precipitate
- filtrationThe precipitate was collected by filtration
- washwashed with EtOAc (5 mL)
- customdried under vacuum
Sources & evidence
- ORD record
- ord-b63ad10d44dd492bb6bfe45d95cb3cad
- Source dataset
- uspto-grants-2015_12
- Patent number
- US09200004B2
Reaction notes
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