Acetic Acid → 6-(2-Chlorophenyl)-7-(4-chlorophenyl)-3-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridine

HRID 1867890Notes

Reaction equation

HRID 1867890 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]([C:30]2[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=2)=[CH:10][C:11]([NH:14][NH:15][C:16](=O)[CH2:17][C:18]2[C:19]([CH3:28])=[N:20][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:22][CH:23]=2)=[N:12][CH:13]=1.C(O)(=O)C>C(O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]([C:30]2[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=2)=[CH:10][C:11]2[N:12]([C:16]([CH2:17][C:18]3[C:19]([CH3:28])=[N:20][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:22][CH:23]=3)=[N:15][N:14]=2)[CH:13]=1

Participants

4

Reactant 2

HCID 176Acetic AcidHCID 57979742N'-(5-(2-chlorophenyl)-4-(4-chlorophenyl)pyridin-2-yl)-2-(2-methyl-6-(trifluoromethyl)pyridin-3-yl)acetohydrazide

Product 1

HCID 119922516-(2-Chlorophenyl)-7-(4-chlorophenyl)-3-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
180 °C

Procedure

A solution of N′-(5-(2-chlorophenyl)-4-(4-chlorophenyl)pyridin-2-yl)-2-(2-methyl-6-(trifluoromethyl)pyridin-3-yl)acetohydrazide (80 mg, 0.15 mmol) and acetic acid (0.5 mL) in ethanol (1 mL) was heated in a microwave oven at 180° C. for 30 min. Analysis by HPLC/MS indicated about 40% of starting material remained. The reaction mixture was heated again in a microwave oven at 180° C. for additional 30 min. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The obtained residue was taken into EtOAc, and the solution was washed with saturated aqueous NaHCO3, saturated aqueous NaCl dried (Na2SO4), filtered and concentrated under reduced pressure. The crude product 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 yield the desired product with about 64% purity. The product was further purified using a silica gel cartridge (12 g) eluting with a gradient of EtOAc (0-70%) in hexanes to afford 18 mg (23%) of the title compound. HPLC/MS (method A): retention time=3.91 min, (M+H)+=513.1.

Workup

  1. temperatureAfter cooling to room temperature
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. washthe solution was washed with saturated aqueous NaHCO3, saturated aqueous NaCl
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified
  8. washEluted with 70% to 100% B, 10 min gradient, 100% B hold for 4 min

Sources & evidence

ORD record
ord-0110acf898174871b95ab447d89d9e21
Source dataset
uspto-grants-2009_12
Patent number
US07632837B2

Reaction notes

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