Triethylamine → 3-(3-Phenylisoxazol-4-yl)-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one

HRID 2089963Notes

Reaction equation

HRID 2089963 reaction equation
[C:1]([C:3]1[C:8](=[O:9])[CH:7]=[CH:6][N:5]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[CH:11]=2)[N:4]=1)#[CH:2].[OH:20][N:21]=[C:22](Cl)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.CCN(CC)CC>C1COCC1>[C:23]1([C:22]2[C:1]([C:3]3[C:8](=[O:9])[CH:7]=[CH:6][N:5]([C:10]4[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[CH:11]=4)[N:4]=3)=[CH:2][O:20][N:21]=2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2756315N-hydroxybenzenecarboximidoyl chlorideHCID 580723393-Ethynyl-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one

Product 1

HCID 580721703-(3-Phenylisoxazol-4-yl)-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-oneYield 55%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-ethynyl-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one (104 mg, 0.391 mmol) and N-hydroxybenzenecarboximidoyl chloride (122 mg, 0.782 mmol) in THF (5 mL) was added Et3N (0.108 mL, 0.782 mmol) at 0° C. The suspension was stirred at room temperature for 14 h. The reaction was quenched with water. The mixture was extracted with AcOEt, washed with brine, dried over Na2SO4, filtered, concentrated in vacuo, purified by column chromatography on silica gel (hexane/AcOEt=50/50 to 0/100) and on basic silica gel (hexane/AcOEt=50/50 to 43/57) and crystallized with AcOEt/heptane to yield the title compound (82.4 mg, 55% yield) as a white solid: mp 217-219° C. 1H NMR (DMSO-d6, 300 MHz): δ ppm 6.87 (1H, d, J=8.0 Hz), 7.50-7.59 (3H, m), 7.86-7.92 (2H, m), 7.94-8.02 (3H, m), 8.15-8.26 (2H, m), 9.09 (1H, d, J=8.2 Hz). Anal. Calcd for C20H12F3N3O2: C, 62.67; H, 3.16; N, 10.96. Found: C, 62.60; H, 3.19; N, 10.95.

Workup

  1. customThe reaction was quenched with water
  2. extractionThe mixture was extracted with AcOEt
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. custompurified by column chromatography on silica gel (hexane/AcOEt=50/50 to 0/100) and on basic silica gel (hexane/AcOEt=50/50 to 43/57)
  8. customcrystallized with AcOEt/heptane

Sources & evidence

ORD record
ord-ab861caf40e14460b51f4b9256c966ce
Source dataset
uspto-grants-2013_05
Patent number
US08435995B2

Reaction notes

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