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

HRID 1805700Notes

Reaction equation

HRID 1805700 reaction equation
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

Participants

9

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 4

HCID 178419072HCID 178419072, compoundCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

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: 1H 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]+.

Workup

  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

Sources & evidence

ORD record
ord-0471258c87a6403a86811ee89799c046
Source dataset
uspto-grants-2013_01
Patent number
US08354411B2

Reaction notes

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