Methanol → 2-[4-[5-Amino-6-(3-phenylisoxazol-5-yl)pyrazin-2-yl]-2-pyridyl]-2-methyl-propanoic acid

HRID 331503Notes

Reaction equation

HRID 331503 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:19]2[CH:24]=[CH:23][N:22]=[C:21]([C:25]([CH3:29])([CH3:28])[C:26]#N)[CH:20]=2)=[N:6][C:7]=1[C:8]1[O:12][N:11]=[C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:9]=1.CO.[OH-:32].[Na+].C(OCC)(=O)C.[OH2:40]>>[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:19]2[CH:24]=[CH:23][N:22]=[C:21]([C:25]([CH3:29])([CH3:28])[C:26]([OH:40])=[O:32])[CH:20]=2)=[N:6][C:7]=1[C:8]1[O:12][N:11]=[C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:9]=1

Participants

5

Reactant 4

HCID 887MethanolHCID 14798Sodium HydroxideHCID 22728543Water ethylacetateHCID 665634872-[4-[5-Amino-6-(3-phenylisoxazol-5-yl)pyrazin-2-yl]-2-pyridyl]-2-methyl-propanenitrile

Product 1

HCID 708186092-[4-[5-Amino-6-(3-phenylisoxazol-5-yl)pyrazin-2-yl]-2-pyridyl]-2-methyl-propanoic acidYield 42%

Conditions

Temperature
110 °C

Procedure

2-[4-[5-amino-6-(3-phenylisoxazol-5-yl)pyrazin-2-yl]-2-pyridyl]-2-methyl-propanenitrile (90 mg, 0.2353 mmol) was added to methanol (3 mL) followed by the addition of 1 M sodium hydroxide (705.9 μL of 1 M, 0.7059 mmol). The mixture was heated in the microwave for 90 minutes at 110° C. The reaction was cooled to ambient temperature and diluted with ethyl acetate/water. The organic layer was washed with brine (×1). The aqueous layer was acidified to pH3 with 1 M hydrochloric acid, extracted with ethyl acetate (×3) and the combined organic extracts washed with brine (×1). The extracted organic layer was dried over MgSO4, filtered and concentrated in vacuo to yield 2-[4-[5-amino-6-(3-phenylisoxazol-5-yl)pyrazin-2-yl]-2-pyridyl]-2-methyl-propanoic acid as white solid (40 mg, 42%) LC/MS m/z 401.1 [M+H]+.

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. washThe organic layer was washed with brine (×1)
  3. extractionextracted with ethyl acetate (×3)
  4. washthe combined organic extracts washed with brine (×1)
  5. dry with materialThe extracted organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ea1619ad4bf944cc85f68bb56ea76318
Source dataset
uspto-grants-2014_11
Patent number
US08877759B2

Reaction notes

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