Acetic Acid → 6-(2-Chlorophenyl)-7-(4-chlorophenyl)-3-(4-(trifluoromethyl)benzyl)-[1,2,4]triazolo[4,3-b]pyridazine

HRID 2266315Notes

Reaction equation

HRID 2266315 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:13]=[N:12][C:11]([NH:14][NH:15][C:16](=O)[CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=2)=[CH:10][C:9]=1[C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=1.C(O)(=O)C>C(O)C.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]([C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=2)=[CH:10][C:11]2[N:12]([C:16]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=3)=[N:15][N:14]=2)[N:13]=1

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 57979748N'-(6-(2-chlorophenyl)-5-(4-chlorophenyl)pyridazin-3-yl)-2-(4-(trifluoromethyl)phenyl)acetohydrazide

Product 1

HCID 119931126-(2-Chlorophenyl)-7-(4-chlorophenyl)-3-(4-(trifluoromethyl)benzyl)-[1,2,4]triazolo[4,3-b]pyridazineYield 83.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of N′-(6-(2-chlorophenyl)-5-(4-chlorophenyl)pyridazin-3-yl)-2-(4-(trifluoromethyl)phenyl)acetohydrazide (124 mg, 0.24 mmol) and acetic acid (69 μL, 1.2 mmol) in ethanol (2.5 mL) in a vial was heated in a microwave oven at 180° C. for 30 min. After cooling to room temperature, the reaction mixture was diluted with EtOAc, washed with saturated aqueous NaHCO3, saturated aqueous NaCl, dried (Na2SO4), filtered and concentrated under reduced pressure. The crude product was purified using a silica gel cartridge (12 g) eluting with a gradient of EtOAc (0-70%) in hexanes to obtain 100 mg of the desired product with 96% purity. The product was crystallized from methanol (2 mL) to yield 42 mg of the pure product as a white solid. The mother liquid was concentrated. The obtained residue was purified using reverse phase preparative HPLC (Conditions: Phenomenex Luna 5μ C18 21.2×100 mm; Eluted with 70% to 100% B, 10 min gradient, 100% B hold for 4 min, (A=90% H2O, 10% MeOH and B=10% H2O, 90% MeOH); Flow rate at 20 mL/min, UV detection at 220 nm) to afford additional 48 mg of the title compound as a white powder (90 mg in total, 75% yield). HPLC/MS (method A): retention time=4.08 min, (M+H)+=499.3.

Workup

  1. washwashed with saturated aqueous NaHCO3, saturated aqueous NaCl
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was purified
  6. washeluting with a gradient of EtOAc (0-70%) in hexanes

Sources & evidence

ORD record
ord-a1baf809a0434bca995d4df4e7d558c1
Source dataset
uspto-grants-2010_12
Patent number
US07858639B2

Reaction notes

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