Dimethylformamide → 3-[1-[4-[2-[1-oxophthalazin-2(1H)-yl]ethoxy]benzyl]-3-phenyl-1H-pyrazol-4-yl]propionic acid

HRID 350276Notes

Reaction equation

HRID 350276 reaction equation
Br[CH2:2][CH2:3][O:4][C:5]1[CH:29]=[CH:28][C:8]([CH2:9][N:10]2[CH:14]=[C:13]([CH2:15][CH2:16][C:17]([O:19]CC)=[O:18])[C:12]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[N:11]2)=[CH:7][CH:6]=1.[C:30]1(=[O:40])[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH:33]=[N:32][NH:31]1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[O:40]=[C:30]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH:33]=[N:32][N:31]1[CH2:2][CH2:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([CH2:9][N:10]2[CH:14]=[C:13]([CH2:15][CH2:16][C:17]([OH:19])=[O:18])[C:12]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[N:11]2)=[CH:28][CH:29]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 83941(2H)-PhthalazinoneHCID 11430Potassium CarbonateHCID 69421065ethyl 3-[1-[4-(2-bromoethoxy)benzyl]-3-phenyl-1H-pyrazol-4-yl]propionate

Product 1

HCID 694215023-[1-[4-[2-[1-oxophthalazin-2(1H)-yl]ethoxy]benzyl]-3-phenyl-1H-pyrazol-4-yl]propionic acidYield 128.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of ethyl 3-[1-[4-(2-bromoethoxy)benzyl]-3-phenyl-1H-pyrazol-4-yl]propionate (1050 mg), 1(2H)-phthalazinone (530 mg), potassium carbonate (1000 mg) and N,N-dimethylformamide (15 ml) was stirred at 90° C. for 5 hours. The reaction mixture was poured into water, and extracted with ethyl acetate. The ethyl acetate layer was washed successively with dilute hydrochloric acid and saturated aqueous sodium chloride solution, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography to obtain a colorless oily substance from the fraction eluted with ethyl acetate-hexane (1:1, volume ratio). After a mixture of the resulting colorless oily substance, 1N aqueous sodium hydroxide solution (5 ml), tetrahydrofuran (5 ml) and ethanol (5 ml) was stirred at room temperature for 3 hours, 1N hydrochloric acid (5 ml) was added to the mixture, and then the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium chloride solution, dried (MgSO4), and concentrated. The resulting colorless crystals were collected by filtration to obtain 3-[1-[4-[2-[1-oxophthalazin-2(1H)-yl]ethoxy]benzyl]-3-phenyl-1H-pyrazol-4-yl]propionic acid (1460 mg, yield 90%). This was recrystallized from acetone-hexane. Melting point: 155–156° C.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe ethyl acetate layer was washed successively with dilute hydrochloric acid and saturated aqueous sodium chloride solution
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customto obtain a colorless oily substance from the fraction
  6. washeluted with ethyl acetate-hexane (1:1, volume ratio)
  7. additionAfter a mixture of the resulting colorless oily substance, 1N aqueous sodium hydroxide solution (5 ml), tetrahydrofuran (5 ml) and ethanol (5 ml)
  8. stirringwas stirred at room temperature for 3 hours
  9. addition1N hydrochloric acid (5 ml) was added to the mixture
  10. extractionthe mixture was extracted with ethyl acetate
  11. washThe ethyl acetate layer was washed with a saturated aqueous sodium chloride solution
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated
  14. filtrationThe resulting colorless crystals were collected by filtration

Sources & evidence

ORD record
ord-df85b99bbda94c3b888ad61663514aa4
Source dataset
uspto-grants-2007_02
Patent number
US07179823B1

Reaction notes

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