Dimethylformamide → 3-amino-N-(4-fluoro-2-hydroxyphenyl)pyrazine-2-carboxamide

HRID 908458Notes

Reaction equation

HRID 908458 reaction equation
[NH2:1][C:2]1[C:3]([C:8]([OH:10])=O)=[N:4][CH:5]=[CH:6][N:7]=1.[NH2:11][C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=1[OH:19].CN(C=O)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(OCC)(=O)C.C(N(CC)CC)C>[NH2:1][C:2]1[C:3]([C:8]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=2[OH:19])=[O:10])=[N:4][CH:5]=[CH:6][N:7]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 726563-Amino-2-pyrazinecarboxylic acidHCID 1857632-Amino-5-fluorophenolHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 1363747323-amino-N-(4-fluoro-2-hydroxyphenyl)pyrazine-2-carboxamideYield 67.3%

Reagents, catalysts & solvents 2

HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-Aminopyrazine-2-carboxylic acid (5 g) and 2-amino-5-fluorophenol (5.9 g) were dissolved into DMF (30 ml). Triethylamine (5.8 g) and HATU (19.2 g) were added to the mixture. The resulting mixture was stirred at room temperature for 24 hours. Ethyl acetate (100 ml) was added to the mixture. The resulting mixture was washed with brine (20 ml×3). The organic phase was dried and concentrated. The resulting residue was purified by chromatography on silica gel to give 3-amino-N-(4-fluoro-2-hydroxyphenyl)pyrazine-2-carboxamide (6 g). NMR Spectrum: (DMSOd6, 400 MHz) 6.60 (m, 2H), 7.50 (br s, 2H), 7.80 (s, 1H), 8.30 (m, 2H), 10.2 (s, 1H), 10.8 (s, 1H); Mass spectrum: MH+ 249.

Workup

  1. washThe resulting mixture was washed with brine (20 ml×3)
  2. customThe organic phase was dried
  3. concentrationconcentrated
  4. customThe resulting residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-fab963135df648e081a934a37eea9263
Source dataset
uspto-grants-2011_09
Patent number
US08017611B2

Reaction notes

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