Salicylaldehyde oxime → 3-(1-Thiophen-2-yl-1H-pyrazol-5-yl)-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one

HRID 1407335ノート

反応式

HRID 1407335 の反応式
C(=NO)C1C(=CC=CC=1)O.C([O-])([O-])=O.[Cs+].[Cs+].[NH:17]1[C:21]([C:22]2[C:27](=[O:28])[CH:26]=[CH:25][N:24]([C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:38])([F:37])[F:36])[CH:30]=3)[N:23]=2)=[CH:20][CH:19]=[N:18]1.I[C:40]1[S:41][CH:42]=[CH:43][CH:44]=1>CC#N.CCOC(C)=O.O.[Cu-]=O>[S:41]1[CH:42]=[CH:43][CH:44]=[C:40]1[N:17]1[C:21]([C:22]2[C:27](=[O:28])[CH:26]=[CH:25][N:24]([C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:37])([F:36])[F:38])[CH:30]=3)[N:23]=2)=[CH:20][CH:19]=[N:18]1

参加物

9

反応物 4

HCID 7200Salicylaldehyde oximeHCID 10796Cesium carbonateHCID 189212-IodothiopheneHCID 594361503-(1H-pyrazol-5-yl)-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one

生成物 1

HCID 580722563-(1-Thiophen-2-yl-1H-pyrazol-5-yl)-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one収率 3%

試薬・触媒・溶媒 4

HCID 178419072HCID 178419072、化合物触媒HCID 962Water溶媒HCID 6342Acetonitrile溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
90 °C

実験手順

To a mixture of copper (I) oxide (0.028 g, 0.20 mmol), salicylaldoxime (0.11 g, 0.78 mmol), Cs2CO3 (0.64 g, 2.0 mmol) and 3-(1H-pyrazol-5-yl)-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one (0.30 g, 0.98 mmol) in MeCN (8 mL) was added 2-iodothiophene (0.16 mL, 1.5 mmol), and the mixture was stirred at 90° C. for 1 day. The mixture was diluted with AcOEt and water, and filtered. The filtrate was partitioned between AcOEt and water. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was chromatographed on silica gel (20/80-100/0 AcOEt/hexane) to give yellow crystals. The crystals were purified by preparative HPLC and recrystallized from AcOEt/hexane to give the title compound (11 mg, 3% yield) as off-white crystals: NMR (300 MHz, CDCl3): δ ppm 6.75 (1H, d, J=7.9 Hz), 6.95 (1H, dd, J=5.5, 3.8 Hz), 7.01 (1H, dd, J=3.8, 1.3 Hz), 7.23 (1H, dd, J=5.5, 1.3 Hz), 7.31 (1H, d, J=8.7 Hz), 7.40 (1H, brs), 7.42 (1H, d, J=1.9 Hz), 7.51-7.57 (1H, m), 7.62 (1H, d, J=7.9 Hz), 7.81 (1H, d, J=1.9 Hz), 8.21 (1H, d, J=7.9 Hz). LC-MS (ESI) m/z 389 [M+H]+.

後処理

  1. filtrationfiltered
  2. customThe filtrate was partitioned between AcOEt and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was chromatographed on silica gel (20/80-100/0 AcOEt/hexane)
  8. customto give yellow crystals
  9. customThe crystals were purified by preparative HPLC
  10. customrecrystallized from AcOEt/hexane

出典と根拠

ORDレコード
ord-a63a88aef6014e289384d616e71ac751
出典データセット
uspto-grants-2014_12
特許番号
US08916566B2

反応ノート

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