Acetohydroxamic Acid → 5-(4-amino-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)benzo[d]isoxazol-3-amine

HRID 475021Notes

Reaction equation

HRID 475021 reaction equation
[NH2:1][C:2]1[C:7]2[C:8]([C:14]3[CH:15]=C[C:17](F)=[C:18]([CH:21]=3)C#N)=[N:9][N:10]([CH:11]([CH3:13])[CH3:12])[C:6]=2[CH:5]=[CH:4][N:3]=1.[OH:23][NH:24][C:25](=O)[CH3:26].CC([O-])(C)C.[K+].C[N:35](C=O)C>>[NH2:1][C:2]1[C:7]2[C:8]([C:14]3[CH:21]=[CH:18][C:17]4[O:23][N:24]=[C:25]([NH2:35])[C:26]=4[CH:15]=3)=[N:9][N:10]([CH:11]([CH3:12])[CH3:13])[C:6]=2[CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 4

HCID 1990Acetohydroxamic Acid2×HCID 6228DimethylformamideHCID 23665647Potassium tert-butoxideHCID 582091125-(4-amino-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-2-fluorobenzonitrile

Product 1

HCID 442037595-(4-amino-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)benzo[d]isoxazol-3-amineYield 55%

Conditions

Temperature
25 °C

Procedure

A mixture of 5-(4-amino-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-2-fluorobenzonitrile (304) (49 mg, 0.166 mmol), N-hydroxyacetamide (compound 305) (18.7 mg, 1.5 eq, 0.249 mmol) and t-BuOK (27.9 mg, 1.5 eq, 0.249 mmol) in DMF (4 mL) was stirred at 25° C. overnight. The mixture was concentrated in vacuo, brine (10 mL) was added and then extracted with ethyl acetate (3×30 mL). The combined organic layer was washed with brine (10 mL), dried over MgSO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography eluting with a mixture of methanol in dichloromethane to afford the desired product, 5-(4-amino-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)benzo[d]isoxazol-3-amine (7) (28 mg, 55% yield) (compound 306) as a white solid. ESI-MS m/z: 309.35 [M+1]+.

Workup

  1. concentrationThe mixture was concentrated in vacuo, brine (10 mL)
  2. additionwas added
  3. extractionextracted with ethyl acetate (3×30 mL)
  4. washThe combined organic layer was washed with brine (10 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was purified by flash column chromatography
  9. washeluting with a mixture of methanol in dichloromethane

Sources & evidence

ORD record
ord-2d6baf214b3a4cde87818f87d6c19b21
Source dataset
uspto-grants-2014_01
Patent number
US08637542B2

Reaction notes

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