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

HRID 499145노트

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HRID 499145 반응식
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]

참가 물질

7

반응물 2

HCID 31374DimethylacetamideHCID 86024941[4-(6-Chloropyridazin-3-yl)piperazin-1-yl]-(2-trifluoromethylphenyl)methanone

생성물 1

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

시약·촉매·용매 4

HCID 11186Zinc cyanide (Zn(CN)2)촉매HCID 23994Zinc촉매HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매

반응 조건

온도
110 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-940aec4d37c54330a09623d8dec2f89c
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07767677B2

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