Water → 7-Methoxy-4-(4-methoxyphenyl)-N-(piperidin-4-yl)phthalazin-1-amine

HRID 30063Notes

Reaction equation

HRID 30063 reaction equation
O.C([N:9]1[CH2:14][CH2:13][CH:12]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH3:27])[CH:24]=3)[C:19]([C:28]3[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=3)=[N:18][N:17]=2)[CH2:11][CH2:10]1)C1C=CC=CC=1>C(O)C.C(O)=O.C(OC(C)C)(C)C.[Pd]>[CH3:27][O:26][C:23]1[CH:24]=[C:25]2[C:20]([C:19]([C:28]3[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=3)=[N:18][N:17]=[C:16]2[NH:15][CH:12]2[CH2:11][CH2:10][NH:9][CH2:14][CH2:13]2)=[CH:21][CH:22]=1

Participants

7

Reactant 2

HCID 962WaterHCID 57691708HCID 57691708, compound2×

Product 1

HCID 576916517-Methoxy-4-(4-methoxyphenyl)-N-(piperidin-4-yl)phthalazin-1-amineYield 97%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 284Formic AcidSolventHCID 702EthanolSolventHCID 7914Diisopropyl EtherSolvent

Conditions

Temperature
85 °C

Procedure

1 g of 10% palladium-on-charcoal and 100 mL of water are introduced into a 500 mL three-necked flask. A solution, prepared beforehand, of 13.3 g of N-(1-benzylpiperidin-4-yl)-7-methoxy-4-(4-methoxyphenyl)phthalazin-1-amine (compound 7) in 50 mL of ethanol and 4.4 mL of formic acid is added dropwise over 1 hour, to this mixture with stirring at 85° C. The reaction mixture is stirred at reflux for 2 hours. After cooling to room temperature, the ethanol is evaporated off under reduced pressure. The mixture is then basified to pH 12 with 2N sodium hydroxide solution and is then extracted with dichloromethane. The organic phase is washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and then evaporated under reduced pressure. The yellow oil obtained is concreted in diisopropyl ether to give a white solid. After filtration and drying under vacuum in the presence of phosphorus pentoxide, 10.29 g of 7-methoxy-4-(4-methoxyphenyl)-N-(piperidin-4-yl)-phthalazin-1-amine are obtained (97% yield).

Workup

  1. customA solution, prepared beforehand
  2. stirringThe reaction mixture is stirred
  3. temperatureat reflux for 2 hours
  4. temperatureAfter cooling to room temperature
  5. customthe ethanol is evaporated off under reduced pressure
  6. extractionis then extracted with dichloromethane
  7. washThe organic phase is washed with saturated aqueous sodium chloride solution
  8. dry with materialdried over anhydrous sodium sulfate
  9. customevaporated under reduced pressure
  10. customThe yellow oil obtained
  11. customto give a white solid
  12. filtrationAfter filtration
  13. dry with materialdrying under vacuum in the presence of phosphorus pentoxide, 10.29 g of 7-methoxy-4-(4-methoxyphenyl)-N-(piperidin-4-yl)-phthalazin-1-amine
  14. customare obtained (97% yield)

Sources & evidence

ORD record
ord-d0b250982e1d4c81ab5498887ad4a31d
Source dataset
uspto-grants-2008_09
Patent number
US07423030B2

Reaction notes

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