Triethylamine → 3-((8-Chloro-4-oxo-3,4-dihydrophthalazin-1-yl)methyl)-5-fluorobenzonitrile

HRID 1091808Notes

Reaction equation

HRID 1091808 reaction equation
[Br-].[Cl:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:11]=1[CH:10]([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)O[C:8]2=[O:31].[F:32][C:33]1[CH:34]=[C:35]([CH:38]=[C:39]([CH:41]=O)[CH:40]=1)[C:36]#[N:37].C(N(CC)CC)C.O.[NH2:51][NH2:52]>CN(C=O)C.CCO.O.C(Cl)Cl>[Cl:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:11]=1[C:10]([CH2:41][C:39]1[CH:38]=[C:35]([CH:34]=[C:33]([F:32])[CH:40]=1)[C:36]#[N:37])=[N:52][NH:51][C:8]2=[O:31]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 24654Hydrazine hydrate (1:1)HCID 447549173-Fluoro-5-formylbenzonitrileHCID 86633041(7-Chloro-3-oxo-1,3-dihydroisobenzofuran-1-yl)triphenylphosphonium bromide

Product 1

HCID 577918013-((8-Chloro-4-oxo-3,4-dihydrophthalazin-1-yl)methyl)-5-fluorobenzonitrileYield 59.9%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

(7-chloro-3-oxo-1,3-dihydroisobenzofuran-1-yl)triphenylphosphonium bromide (101) (2.88 g, 6.71 mmol) and 3-fluoro-5-formylbenzonitrile (1.0 g, 6.71 mmol) were dissolved DCM (60 mL), to this was added triethylamine (1.215 mL, 8.72 mmol) and the reaction was stirred overnight. The reaction mixture was evaporated to afford a brown solid. To this was added water (40 mL), EtOH (40 mL) and DMF (4 mL). Hydrazine hydrate (3.36 g, 67.06 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 yellow solid (1.260 g, 59.9% yield), which was used without further purification; 1H NMR (400.132 MHz, DMSO) δ 4.68 (2H, s), 7.49 (1H, d), 7.58 (1H, s), 7.68 (1H, d), 7.82 (1H, t), 7.99 (1H, dd), 8.34 (1H, dd), 12.82 (1H, s); m/z (LC-MS, ESI−), RT=2.21 (M−H 312).

Workup

  1. customThe reaction mixture was evaporated
  2. customto afford a brown 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-140c4d4c25c2402da9716be9fc007d82
Source dataset
uspto-grants-2012_03
Patent number
US08129380B2

Reaction notes

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