Water → 5-(Cyclopropylmethoxy)-3-(1-phenyl-1H-pyrazol-5-yl)-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one

HRID 1407283Notes

Reaction equation

HRID 1407283 reaction equation
[OH:1][C:2]1[C:3](=[O:29])[C:4]([C:18]2[N:22]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[N:21]=[CH:20][CH:19]=2)=[N:5][N:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)[CH:7]=1.Br[CH2:31][CH:32]1[CH2:34][CH2:33]1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[CH:32]1([CH2:31][O:1][C:2]2[C:3](=[O:29])[C:4]([C:18]3[N:22]([C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=4)[N:21]=[CH:20][CH:19]=3)=[N:5][N:6]([C:8]3[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:16])([F:15])[F:17])[CH:9]=3)[CH:7]=2)[CH2:34][CH2:33]1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 81503BromomethylcyclopropaneHCID 594362225-Hydroxy-3-(1-phenyl-1H-pyrazol-5-yl)-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one

Product 1

HCID 594362775-(Cyclopropylmethoxy)-3-(1-phenyl-1H-pyrazol-5-yl)-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-oneYield 91.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of 5-hydroxy-3-(1-phenyl-1H-pyrazol-5-yl)-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one (100 mg, 0.25 mmol), (bromomethyl)cyclopropane (0.048 mL, 0.50 mmol), and K2CO3 (104 mg, 0.75 mmol) in DMF (1 mL) was stirred for 20 h at room temperature. The reaction mixture was poured into water and extracted with AcOEt. The extract was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography eluting with hexane/AcOEt (1/1) and crystallized from MeOH to give the title compound (103 mg, 91% yield) as colorless prisms: mp 72-78° C.; 1H NMR (300 MHz, CDCl3): δ ppm 0.32-0.47 (2H, m), 0.60-0.76 (2H, m), 1.26-1.39 (1H, m), 4.06 (2H, d, J=7.2 Hz), 7.04 (1H, dd, J=2.3, 8.3 Hz), 7.18 (1H, s), 7.33-7.46 (7H, m), 7.55 (1H, d, J=7.9 Hz), 7.80 (1H, d, J=1.9 Hz), 7.99 (1H, s). LC-MS (ESI) m/z 453 [M+H]+. Anal. Calcd for C24H19F3N4O2.0.5H2O: C, 62.47; H, 4.37; N, 12.14. Found: C, 62.19; H, 4.41; N, 12.15.

Workup

  1. extractionextracted with AcOEt
  2. washThe extract was washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by basic silica gel column chromatography
  6. washeluting with hexane/AcOEt (1/1)
  7. customcrystallized from MeOH

Sources & evidence

ORD record
ord-267e08dbb48842999581e807677167e4
Source dataset
uspto-grants-2014_12
Patent number
US08916566B2

Reaction notes

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