Triethylamine → 2-Fluoro-5-((8-methoxy-4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzonitrile

HRID 1091804Notes

Reaction equation

HRID 1091804 reaction equation
[Br-].[CH3:2][O:3][C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[CH:11]([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)O[C:9]2=[O:32].[F:33][C:34]1[CH:41]=[CH:40][C:39]([CH:42]=O)=[CH:38][C:35]=1[C:36]#[N:37].C(N(CC)CC)C.O.[NH2:52][NH2:53]>CN(C=O)C.CCO.O.C(Cl)Cl>[F:33][C:34]1[CH:41]=[CH:40][C:39]([CH2:42][C:11]2[C:12]3[C:8](=[CH:7][CH:6]=[CH:5][C:4]=3[O:3][CH3:2])[C:9](=[O:32])[NH:53][N:52]=2)=[CH:38][C:35]=1[C:36]#[N:37]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 24654Hydrazine hydrate (1:1)HCID 27695822-Fluoro-5-formylbenzonitrileHCID 11720320(7-Methoxy-3-oxo-1,3-dihydroisobenzofuran-1-yl)triphenylphosphonium bromide

Product 1

HCID 577918302-Fluoro-5-((8-methoxy-4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzonitrileYield 126%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

(7-methoxy-3-oxo-1,3-dihydroisobenzofuran-1-yl)triphenylphosphonium bromide (123) (3.5 g, 6.93 mmol) and 2-fluoro-5-formylbenzonitrile (1.033 g, 6.93 mmol) were dissolved DCM (30 mL), to this was added triethylamine (1.255 mL, 9.00 mmol) and the reaction was stirred overnight. The solvent was removed to afford a white solid. To this was added water (20 mL), EtOH (20 mL) and DMF (2 mL). Hydrazine hydrate (3.36 mL, 69.26 mmol) was added and the reaction was heated at reflux overnight. The reaction was cooled and the precipitate was collected by filtration, washed with EtOH (25 mL) and air dried to afford the desired material as a white solid (2.70 g, >100%), which was used without further purification; 1H NMR (400.132 MHz, DMSO) δ 3.79 (3H, s), 4.40 (2H, s), 7.31-7.39 (1H, m), 7.47-7.59 (2H, m), 7.66-7.73 (2H, m), 7.78-7.82 (1H, m), 12.40-12.62 (1H, m).

Workup

  1. customThe solvent was removed
  2. customto afford a white solid
  3. temperaturethe reaction was heated
  4. temperatureat reflux overnight
  5. temperatureThe reaction was cooled
  6. filtrationthe precipitate was collected by filtration
  7. washwashed with EtOH (25 mL) and air
  8. customdried

Sources & evidence

ORD record
ord-eaeccd99e7fe4119ac7e609350083347
Source dataset
uspto-grants-2012_03
Patent number
US08129380B2

Reaction notes

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