Potassium Carbonate → 2-(4-(trifluoromethyl)benzyl)-6-(2-chlorophenyl)-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one

HRID 2250346Notes

Reaction equation

HRID 2250346 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)=[CH:10][C:11]2[N:12]([C:14](=[O:17])[NH:15][N:16]=2)[N:13]=1.[F:25][C:26]([F:36])([F:35])[C:27]1[CH:34]=[CH:33][C:30]([CH2:31]Br)=[CH:29][CH:28]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[F:25][C:26]([F:35])([F:36])[C:27]1[CH:34]=[CH:33][C:30]([CH2:31][N:15]2[C:14](=[O:17])[N:12]3[N:13]=[C:8]([C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=4[Cl:1])[C:9]([C:18]4[CH:19]=[CH:20][C:21]([Cl:24])=[CH:22][CH:23]=4)=[CH:10][C:11]3=[N:16]2)=[CH:29][CH:28]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 1230621-(Bromomethyl)-4-(trifluoromethyl)benzeneHCID 596416776-(2-chlorophenyl)-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one

Product 1

HCID 156035292-(4-(trifluoromethyl)benzyl)-6-(2-chlorophenyl)-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-oneYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 6-(2-chlorophenyl)-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (18 mg, 0.05 mmol) and 4-trifluoromethyl benzylbromide (18 mg, 0.075 mmol) in anhydrous DMF (0.5 mL)) at 70° C. was added solid K2CO3 (13.8 mg, 0.1 mmol). After addition, the reaction mixture was stirred at 70° C. for 30 min. Analysis by HPLC/MS indicated the starting material had been consumed. After cooling to room temperature, the reaction was diluted with water, and extracted with EtOAc (5 mL×3). The combined EtOAc extracts were washed with saturated aqueous NaCl, dried (Na2SO4), filtered and concentrated under reduced pressure. The obtained residue was purified using reverse phase preparative HPLC (Conditions: Phenomenex Luna 5 μ C18 21.2×100 mm; Eluted with 70% to 100% B, 8 min gradient, hold at 100% B for 6 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 18 mg (70%) of the title compound as a yellow powder. LC/MS (method A): retention time=4.05 min, (M+H)+=515. 1H NMR (CDCl3, 400 MHz): δ 7.57-7.70 (m, 4H), 7.42-7.48 (m, 1H), 7.41 (s, 1H), 7.30-7.38 (m, 2H), 7.17-7.25 (m, 3H), 7.02 (d,J=8.0 Hz, 2H), 5.30 (s, 2H).

Workup

  1. additionAfter addition
  2. customhad been consumed
  3. temperatureAfter cooling to room temperature
  4. additionthe reaction was diluted with water
  5. extractionextracted with EtOAc (5 mL×3)
  6. washThe combined EtOAc extracts were washed with saturated aqueous NaCl
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe obtained residue was purified
  11. washEluted with 70% to 100% B, 8 min gradient
  12. waithold at 100% B for 6 min

Sources & evidence

ORD record
ord-80bcad0e77f34e76b9f8cc66efe9b6e5
Source dataset
uspto-grants-2008_01
Patent number
US07317012B2

Reaction notes

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