Ethyl Acetate → 4-(Trifluoromethyl)benzyl-8-chloro-7-(4-chlorophenyl)-2H-[1,2,4]triazolo[4,3-b]pyridazin-3-one

HRID 2224281Notes

Reaction equation

HRID 2224281 reaction equation
[Cl:1][C:2]1[C:3]2[N:4]([C:15](=[O:18])[NH:16][N:17]=2)[N:5]=[CH:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=1.[F:19][C:20]([F:30])([F:29])[C:21]1[CH:28]=[CH:27][C:24]([CH2:25]Br)=[CH:23][CH:22]=1.C([O-])([O-])=O.[K+].[K+].CCOC(C)=O>CN(C=O)C>[F:19][C:20]([F:29])([F:30])[C:21]1[CH:28]=[CH:27][C:24]([CH2:25][N:16]2[C:15](=[O:18])[N:4]3[N:5]=[CH:6][C:7]([C:8]4[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=4)=[C:2]([Cl:1])[C:3]3=[N:17]2)=[CH:23][CH:22]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 1230621-(Bromomethyl)-4-(trifluoromethyl)benzeneHCID 597166868-chloro-7-(4-chlorophenyl)-2H-[1,2,4]triazolo[4,3-b]pyridazin-3-one

Product 1

HCID 597166974-(Trifluoromethyl)benzyl-8-chloro-7-(4-chlorophenyl)-2H-[1,2,4]triazolo[4,3-b]pyridazin-3-oneYield 74%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

To a stirring suspension of 8-chloro-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (1.12 g, 4.0 mmol) and 4-(trifluoromethyl)benzyl bromide (1.24 g, 5.2 mmol) in DMF (15 mL) at RT under argon was added K2CO3 (0.83 g, 5.2 mmol). The resulting mixture was heated at 55° C. for 2 h. After 2 h, HPLC/MS analysis indicated the reaction was complete. The reaction mixture was cooled to RT and EtOAc (100 mL) was added. The resulting mixture was washed with saturated NaCl (50 mL×2). The organic layer was dried (Na2SO4), filtered and concentrated under vacuum with co-evaporation of toluene (10 mL×2) to obtain a dark yellow solid. This crude product was washed with MeOH (10 mL×2), then dried under vacuum at room temperature for 3 h to obtain the title compound, 2-(4-(trifluoromethyl)benzyl)-8-chloro-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (1.3 g, 74%) as a yellow solid. MS [M+H]+ 439; HPLC retention time=3.92 min; 1HNMR (400 MHz, CDCl3) δ 9.00 (s, 1H), 7.45-7.61 (m, 8H), 5.32 (s, 2H).

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. washThe resulting mixture was washed with saturated NaCl (50 mL×2)
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum with co-evaporation of toluene (10 mL×2)
  6. customto obtain a dark yellow solid
  7. washThis crude product was washed with MeOH (10 mL×2)
  8. customdried under vacuum at room temperature for 3 h

Sources & evidence

ORD record
ord-9a4256607ad34da09bd7c7cf6acad2e2
Source dataset
uspto-grants-2008_05
Patent number
US07378418B2

Reaction notes

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