4-Hydroxybenzaldehyde → HCID 178486396, compound

HRID 253218Notes

Reaction equation

HRID 253218 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]([C:14](=O)[CH:15]([CH3:17])[CH3:16])[C:12]#[N:13])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[NH2:19][NH2:20].[OH:21][C:22]1[CH:29]=[CH:28][C:25]([CH:26]=O)=[CH:24][CH:23]=1.[F:30][C:31]([F:36])([F:35])[C:32]([OH:34])=[O:33]>C(O)C>[F:30][C:31]([F:36])([F:35])[C:32]([OH:34])=[O:33].[CH3:16][CH:15]([C:14]1[C:11]2[C:5]3[CH:4]=[C:3]([O:2][CH3:1])[C:8]([O:9][CH3:10])=[CH:7][C:6]=3[C:26]([C:25]3[CH:28]=[CH:29][C:22]([OH:21])=[CH:23][CH:24]=3)=[N:13][C:12]=2[NH:20][N:19]=1)[CH3:17]

Participants

6

Reactant 4

HCID 1264-HydroxybenzaldehydeHCID 6422Trifluoroacetic acidHCID 9321HydrazineHCID 43157030HCID 43157030, compound

Product 1

HCID 178486396HCID 178486396, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

2-[3,4-bis(methyloxy)phenyl]-4-methyl-3-oxopentanenitrile (100 mg, 0.40 mmol) was dissolved in ethanol (1 mL), and anhydrous hydrazine (98%, 16 μL, 0.52 mmol) was added. The resulting mixture was heated at reflux for 1 hour. It was cooled, concentrated, and the residue was dried in vacuum for one hour. To this residue was added of 4-hydroxybenzaldehyde (74 mg, 0.61 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 and lyophillization of the pure fractions 4-[1-(1-methylethyl)-7,8-bis(methyloxy)-3H-pyrazolo[3,4-c]isoquinolin-5-yl]phenol trifluoroacetic acid salt (60 mg, 0.13 mmol, 33% yield) was obtained. 1H NMR (400 MHz, d6-DMSO): 7.62-7.60 (d, 2H), 7.58 (s, 1H), 7.55 (s, 1H), 6.98-6.96 (d, 2H), 4.04 (s, 3H), 3.77-3.75 (m, 1H), 3.76 (s, 3H), 1.49-1.46 (d, 2H); MS (EI) for C21H21N3O3: 363 (MH+).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 1 hour
  3. temperatureIt was cooled
  4. concentrationconcentrated
  5. customthe residue was dried in vacuum for one hour
  6. concentrationThen the reaction mixture was concentrated
  7. dissolutiondissolved in 10 mL of N,N-dimethylformamide
  8. custompurified by preparatory HPLC (Shimadzu LC-8A HPLC, Waters Xterra C18 30 mm×100 mm column, acetonitrile-water-trifluoroacetic eluent)

Sources & evidence

ORD record
ord-e12cf4c2798e4134b75f78cf9c6002cf
Source dataset
uspto-grants-2011_01
Patent number
US07872014B2

Reaction notes

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