Dimethylacetamide → 6-[4-(2-Trifluoromethylbenzoyl)piperazin-1-yl]pyridazine-3-carbonitrile

HRID 499145Notes

Reaction equation

HRID 499145 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:22]([F:25])([F:24])[F:23])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C[C:27]([N:29](C)C)=O>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[Zn].[C-]#N.[C-]#N.[Zn+2]>[F:23][C:22]([F:25])([F:24])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[C:14]([N:11]1[CH2:12][CH2:13][N:8]([C:5]2[N:6]=[N:7][C:2]([C:27]#[N:29])=[CH:3][CH:4]=2)[CH2:9][CH2:10]1)=[O:15]

Participants

7

Reactant 2

HCID 31374DimethylacetamideHCID 86024941HCID 86024941, compound

Product 1

HCID 675233306-[4-(2-Trifluoromethylbenzoyl)piperazin-1-yl]pyridazine-3-carbonitrileYield 59%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
110 °C

Procedure

In an oven dried round-bottom flask, [4-(6-chloropyridazin-3-yl)piperazin-1-yl]-(2-trifluoromethylphenyl)methanone (1.80 g, 4.85 mmol), Pd2(dba)3 (0.130 g, 0.14 mmol), 1,1′-bis(diphenylphosphino)ferrocene (0.161 g, 0.29 mmol), Zn powder (0.317 g, 4.85 mmol) and Zn(CN)2 (0.569 g, 4.85 mmol) were placed under nitrogen atmosphere. Dimethylacetamide (10 mL) was added and the suspension was purged with nitrogen. The mixture was then heated at 110° C. overnight, then cooled to room temperature and then concentrated in vacuo. The brown residue was dissolved in ethyl acetate (15 mL) and washed with water (2×10 mL), dried over anhydrous Na2SO4 and then concentrated. The crude product was purified using column chromatography to afford 6-[4-(2-trifluoromethylbenzoyl)piperazin-1-yl]pyridazine-3-carbonitrile as a pale yellow syrup in 59% yield (1.03 g). 1H NMR (300 MHz, CDCl3) δ 7.71 (d, J=7.8 Hz, 1H), 7.63-7.50 (m, 2H), 7.48 (d, J=9.6 Hz, 1H), 7.32 (d, J=7.3 Hz, 1H), 6.89 (d, J=9.6 Hz, 1H), 4.12-3.98 (m, 1H), 3.92-3.70 (m, 5H), 3.31 (t, J=5.3 Hz, 2H), 13C NMR (75 MHz, CDCl3) δ 167.7, 158.4, 132.4, 130.8, 130.0, 129.6, 127.1, 126.9, 126.8, 116.5, 110.2, 46.2, 44.2, 43.9, 41.1. MS (ES+) m/z 362.3 (M+H).

Workup

  1. customthe suspension was purged with nitrogen
  2. temperaturecooled to room temperature
  3. concentrationconcentrated in vacuo
  4. dissolutionThe brown residue was dissolved in ethyl acetate (15 mL)
  5. washwashed with water (2×10 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated
  8. customThe crude product was purified

Sources & evidence

ORD record
ord-940aec4d37c54330a09623d8dec2f89c
Source dataset
uspto-grants-2010_08
Patent number
US07767677B2

Reaction notes

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