4-Aminophenol → 4-(1-benzyloxymethyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)aniline

HRID 2070019Notes

Reaction equation

HRID 2070019 reaction equation
[CH:1]1[C:6]([NH2:7])=[CH:5][CH:4]=[C:3]([OH:8])[CH:2]=1.CC(C)([O-])C.[K+].C(=O)([O-])[O-].[K+].[K+].[CH2:21]([O:28][CH2:29][N:30]1[C:34]2=[N:35][CH:36]=[CH:37][C:38](Cl)=[C:33]2[CH:32]=[N:31]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>CN1C(=O)CCC1.O>[CH2:21]([O:28][CH2:29][N:30]1[C:34]2=[N:35][CH:36]=[CH:37][C:38]([O:8][C:3]3[CH:4]=[CH:5][C:6]([NH2:7])=[CH:1][CH:2]=3)=[C:33]2[CH:32]=[N:31]1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

7

Reactant 4

HCID 4034-AminophenolHCID 11430Potassium CarbonateHCID 23665647Potassium tert-butoxideHCID 593985441-benzyloxymethyl-4-chloro-1H-pyrazolo[3,4-b]pyridine

Product 1

HCID 593985194-(1-benzyloxymethyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)anilineYield 56.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

P-Aminophenol (800 mg, 7.33 mmol) and potassium t-butoxide (820 mg, 7.31 mmol) were dissolved in NMP (10 mL), and potassium carbonate (510 mg, 3.69 mmol) was added thereto. The resulting mixture was stirred at room temperature for 1 hour, and 1-benzyloxymethyl-4-chloro-1H-pyrazolo[3,4-b]pyridine (860 mg, 5.62 mmol) was added thereto. The resulting mixture was stirred at 80° C. for 0.5 hours. The reaction container was cooled, and the content was diluted with water (100 mL) and extracted with ethyl acetate (100 mL) three times. The combined organic layer was washed with saturated brine (50 mL) twice, dried, and concentrated. The residue was purified by silica-gel column chromatography (Fuji Silysia, BW300, 30 g, n-hexane:EtOAc=1:1) to give 4-(1-benzyloxymethyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)aniline as a light-yellow syrup (1105 mg, yield: quantitative).

Workup

  1. stirringThe resulting mixture was stirred at 80° C. for 0.5 hours
  2. temperatureThe reaction container was cooled
  3. extractionextracted with ethyl acetate (100 mL) three times
  4. washThe combined organic layer was washed with saturated brine (50 mL) twice
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was purified by silica-gel column chromatography (Fuji Silysia, BW300, 30 g, n-hexane:EtOAc=1:1)

Sources & evidence

ORD record
ord-4e76097cdcb44a4eb34c07d1128f8174
Source dataset
uspto-grants-2012_10
Patent number
US08299252B2

Reaction notes

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