Methanol → 1-[2-Fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]piperazine-2,6-dione

HRID 459774Notes

Reaction equation

HRID 459774 reaction equation
C([O-])=O.[NH4+].C([N:12]1[CH2:17][C:16](=[O:18])[N:15]([C:19]2[CH:24]=[C:23]([CH2:25][C:26]3[C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[C:29](=[O:36])[NH:28][N:27]=3)[CH:22]=[CH:21][C:20]=2[F:37])[C:14](=[O:38])[CH2:13]1)C1C=CC=CC=1.CO>O.[Pd]>[F:37][C:20]1[CH:21]=[CH:22][C:23]([CH2:25][C:26]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[C:29](=[O:36])[NH:28][N:27]=2)=[CH:24][C:19]=1[N:15]1[C:14](=[O:38])[CH2:13][NH:12][CH2:17][C:16]1=[O:18]

Participants

6

Reactant 3

HCID 887MethanolHCID 2723923Ammonium formateHCID 184443764-Benzyl-1-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]piperazine-2,6-dione

Product 1

HCID 184443391-[2-Fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]piperazine-2,6-dione

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 962WaterSolvent

Procedure

A solution of ammonium formate (0.55 g, 8.8 mmol) in water (5 ml) was added to a stirred mixture of 4-benzyl-1-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]piperazine-2,6-dione (1 g, 2.2 mmol; prepared in a manner similar to that described in Example 31), 10% palladium on carbon catalyst (0.33 g) and methanol (15 ml), the mixture was heated under reflux for 1 hour, then it was cooled to ambient temperature and filtered through a pad of Celite filter aid. The filter pad was washed with methanol (50 ml), then the combined filtrate and washings were concentrated in vacuo. The residue was diluted with water (20 ml), the product was extracted into ethyl acetate (4×20 ml), the combined extracts were dried (MgSO4) and the solvent was removed in vacuo to give 1-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]piperazine-2,6-dione (0.8 g) as a pale brown solid, 250 MHz 1H-nmr (d6-DMSO) δ (ppm): 3.3 (2× overlapping d, 4H) (2×ring CH2), 4.25 (s, 2H) (ArCH2—), 6.95–7.2 (m, 2H) (2×ArH), 7.7–7.9 (m, 3H) (3×ArH), 7.95 (d, 1H) (ArH), 8.2 (d, 1H) (ArH), 9.7 (s, 1H) (piperazine NH), 12.6 (s, 1H) (CONH).

Workup

  1. customprepared in a manner similar to
  2. temperaturethe mixture was heated
  3. temperatureunder reflux for 1 hour
  4. filtrationfiltered through a pad of Celite
  5. filtrationfilter aid
  6. washThe filter pad was washed with methanol (50 ml)
  7. concentrationthe combined filtrate and washings were concentrated in vacuo
  8. additionThe residue was diluted with water (20 ml)
  9. extractionthe product was extracted into ethyl acetate (4×20 ml)
  10. dry with materialthe combined extracts were dried (MgSO4)
  11. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-dff40e71dbfa45b884a3263e0d6d0ff9
Source dataset
uspto-grants-2007_03
Patent number
US07196085B2

Reaction notes

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