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

HRID 499145ノート

反応式

HRID 499145 の反応式
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]

参加物

7

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 4

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

反応条件

温度
110 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-940aec4d37c54330a09623d8dec2f89c
出典データセット
uspto-grants-2010_08
特許番号
US07767677B2

反応ノート

読み込み中…