4-Hydroxybenzaldehyde → 4-(1-methyl-3H-pyrazolo[3,4-c]isoquinolin-5-yl)phenol

HRID 253224Notes

Reaction equation

HRID 253224 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[C:5]([NH2:13])[NH:4][N:3]=1.[OH:14][C:15]1[CH:22]=[CH:21][C:18]([CH:19]=O)=[CH:17][CH:16]=1.CS(O)(=O)=O>C(OCC)(=O)C>[CH3:1][C:2]1[C:6]2[C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[C:19]([C:18]3[CH:21]=[CH:22][C:15]([OH:14])=[CH:16][CH:17]=3)=[N:13][C:5]=2[NH:4][N:3]=1

Participants

5

Reactant 3

HCID 1264-HydroxybenzaldehydeHCID 6395Methanesulfonic AcidHCID 178434634HCID 178434634, compound

Product 1

HCID 1784343834-(1-methyl-3H-pyrazolo[3,4-c]isoquinolin-5-yl)phenolYield 15%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To 3-methyl-4-phenyl-1H-pyrazol-5-amine (173 mg, 1 mmol) was added 4-hydroxybezaldehyde (244 mg, 2 mmol) and methanesulfonic acid (3 mL). The mixture was heated to 120° C. for 16 h. After cooling to rt, the mixture was diluted with ethyl acetate and then filtered through celite. The product was then extracted from the organic phase with NaOH (aq). The organic phase was discarded, and the aqueous extract was carefully neutralized with HCl (conc) and then extracted with ethyl acetate. The ethyl acetate extract was dried over sodium sulfate, filtered, and concentrated in vacuo. The crude residue was purified by flash chromatography (ethyl acetate) to provide 41.2 mg of 4-(1-methyl-3H-pyrazolo[3,4-c]isoquinolin-5-yl)phenol (0.15 mmol, 15% yield). 1H-NMR (400 MHz, DMSO-d6): δ13.42 (s, 1H), 9.81 (s, 1H), 8.34 (d, 1H), 8.11 (d, 1H), 7.87 (t, 1H), 7.50 (d, 2H), 6.94 (d, 2H), 2.79 (s, 3H); MS (EI) for C17H13N3O: 276 (MH+).

Workup

  1. temperatureAfter cooling to rt
  2. filtrationfiltered through celite
  3. extractionThe product was then extracted from the organic phase with NaOH (aq)
  4. extractionthe aqueous extract
  5. extractionextracted with ethyl acetate
  6. extractionThe ethyl acetate extract
  7. dry with materialwas dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude residue was purified by flash chromatography (ethyl acetate)

Sources & evidence

ORD record
ord-983e25a5cac448d2a14c7e406e468886
Source dataset
uspto-grants-2011_01
Patent number
US07872014B2

Reaction notes

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