Potassium Carbonate → 5-Methoxy-1-(2,2,3,3,7-pentafluoro-2,3-dihydro-1,4-benzodioxin-6-yl)-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

HRID 1624786Notes

Reaction equation

HRID 1624786 reaction equation
Br[C:2]1[C:7](=[O:8])[C:6]([O:9][CH3:10])=[CH:5][N:4]([C:11]2[C:24]([F:25])=[CH:23][C:14]3[O:15][C:16]([F:22])([F:21])[C:17]([F:20])([F:19])[O:18][C:13]=3[CH:12]=2)[N:3]=1.[C:26]1([N:32]2[C:36](B3OC(C)(C)C(C)(C)O3)=[CH:35][CH:34]=[N:33]2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.O.[Cl-].[Na+].O.C([O-])(O)=O.[Na+]>[CH3:10][O:9][C:6]1[C:7](=[O:8])[C:2]([C:36]2[N:32]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[N:33]=[CH:34][CH:35]=2)=[N:3][N:4]([C:11]2[C:24]([F:25])=[CH:23][C:14]3[O:15][C:16]([F:22])([F:21])[C:17]([F:20])([F:19])[O:18][C:13]=3[CH:12]=2)[CH:5]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 580723671-Phenyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 594361513-bromo-5-methoxy-1-(2,2,3,3,7-pentafluoro-2,3-dihydro-1,4-benzodioxin-6-yl)pyridazin-4(1H)-one

Product 1

HCID 580725295-Methoxy-1-(2,2,3,3,7-pentafluoro-2,3-dihydro-1,4-benzodioxin-6-yl)-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-oneYield 66%

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 516892Sodium BicarbonateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A mixture of 3-bromo-5-methoxy-1-(2,2,3,3,7-pentafluoro-2,3-dihydro-1,4-benzodioxin-6-yl)pyridazin-4(1H)-one (200 mg, 0.466 mmol), 1-phenyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (189 mg, 0.699 mmol), K2CO3 (129 mg, 0.932 mmol) and PdCl2{P(t-Bu)2(Ph-p-NMe2)}2 (16.5 mg, 0.0233 mmol) in toluene (2.3 mL) and water (0.23 mL) was heated to reflux for 20 h under Ar. The mixture was diluted with water, brine and saturated NaHCO3 aqueous solution, extracted with AcOEt, dried over Na2SO4, filtered, concentrated in vacuo, purified by column chromatography on basic silica gel (hexane/AcOEt=50/50 to 0/100) and recrystallized with AcOEt/hexane to yield the title compound (150 mg, 66% yield) as a white solid: mp 192-194° C. 1H NMR (DMSO-d6, 300 MHz): δ ppm 3.76 (3H, s), 7.00 (1H, d, J=1.9 Hz), 7.28-7.48 (6H, m), 7.79 (1H, d, J=1.9 Hz), 7.93 (1H, d, J=10.5 Hz), 8.51 (1H, d, J=1.9 Hz). Anal. Calcd for C22H13F5N4O4: C, 53.67; H, 2.66; N, 11.38. Found: C, 53.73; H, 2.72; N, 11.33.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 20 h under Ar
  3. extractionextracted with AcOEt
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. custompurified by column chromatography on basic silica gel (hexane/AcOEt=50/50 to 0/100)
  8. customrecrystallized with AcOEt/hexane

Sources & evidence

ORD record
ord-928fa636702c460a816a65e0a36f4885
Source dataset
uspto-grants-2014_07
Patent number
US08778944B2

Reaction notes

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