4-Hydroxybenzaldehyde → HCID 178486397, compound

HRID 253216Notes

Reaction equation

HRID 253216 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]([C:14](=O)[C:15]([F:18])([F:17])[F:16])[C:12]#[N:13])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[NH2:20][NH2:21].[OH:22][C:23]1[CH:30]=[CH:29][C:26]([CH:27]=O)=[CH:25][CH:24]=1.[F:31][C:32]([F:37])([F:36])[C:33]([OH:35])=[O:34]>C1C=CC=CC=1.C(O)(=O)C>[F:31][C:32]([F:37])([F:36])[C:33]([OH:35])=[O:34].[CH3:10][O:9][C:8]1[C:3]([O:2][CH3:1])=[CH:4][C:5]2[C:11]3[C:14]([C:15]([F:18])([F:17])[F:16])=[N:21][NH:20][C:12]=3[N:13]=[C:27]([C:26]3[CH:29]=[CH:30][C:23]([OH:22])=[CH:24][CH:25]=3)[C:6]=2[CH:7]=1

Participants

7

Reactant 4

HCID 1264-HydroxybenzaldehydeHCID 6422Trifluoroacetic acidHCID 9321HydrazineHCID 15613830HCID 15613830, compound

Product 1

HCID 178486397HCID 178486397, compoundYield 30%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 241BenzeneSolvent

Conditions

Temperature
70 °C

Procedure

2-[3,4-bis(methyloxy)phenyl]4,4,4-trifluoro-3-oxobutanenitrile (100 mg, 0.37 mmol) was dissolved in benzene (10 mL), acetic acid (1 mL), and anhydrous hydrazine (98%, 12 μL, 0.44 mmol). The resulting mixture was heated at reflux for 3 hours. It was cooled, concentrated, and the residue was basified with solid sodium bicarbonate, diluted with ethyl acetate (50 mL), washed with water and brine (50 mL each), dried over sodium sulfate, filtered, concentrated, and the residue was dried in vacuum to give an oily residue. To this residue was added of 4-hydroxybenzaldehyde (67 mg, 0.55 mmol) and trifluoroacetic acid (1 mL), and the mixture was heated at 70° C. for 18 hours. Then the reaction mixture was concentrated, dissolved in 10 mL of N,N-dimethylformamide and purified by preparatory HPLC (Shimadzu LC-8A HPLC, Waters Xterra C18 30 mm×100 mm column, acetonitrile-water-trifluoroacetic eluent). After concentration then then lyophillization of the pure fractions 4-[7,8-bis(methyloxy)-1-(trifluoromethyl)-3H-pyrazolo[3,4-c]isoquinolin-5-yl]phenol trifluoroacetic acid salt (56 mg, 0.11 mmol, 30% yield) was obtained. 1H NMR (400 MHz, d6-DMSO): 7.63-7.61 (d, 2H), 7.59 (s, 1H), 7.58 (s, 1H), 6.99-6.97 (d, 2H), 4.00 (s, 3H), 3.80 (s, 3H); MS (EI) for C19H14N3O3F3: 340 (MH+).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 3 hours
  3. temperatureIt was cooled
  4. concentrationconcentrated
  5. additiondiluted with ethyl acetate (50 mL)
  6. washwashed with water and brine (50 mL each)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customthe residue was dried in vacuum
  11. customto give an oily residue
  12. concentrationThen the reaction mixture was concentrated
  13. dissolutiondissolved in 10 mL of N,N-dimethylformamide
  14. custompurified by preparatory HPLC (Shimadzu LC-8A HPLC, Waters Xterra C18 30 mm×100 mm column, acetonitrile-water-trifluoroacetic eluent)
  15. concentrationAfter concentration

Sources & evidence

ORD record
ord-2d9aac9521bb42ba97670853dec0323a
Source dataset
uspto-grants-2011_01
Patent number
US07872014B2

Reaction notes

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