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

HRID 2250349Notes

Reaction equation

HRID 2250349 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:31])([F:30])[CH2:27][CH2:28]I.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C(#N)C>[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:19]=[CH:20][C:21]([Cl:24])=[CH:22][CH:23]=2)=[CH:10][C:11]2[N:12]([C:14](=[O:17])[N:15]([CH2:28][CH2:27][C:26]([F:31])([F:30])[F:25])[N:16]=2)[N:13]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 1561651,1,1-Trifluoro-3-iodopropane2×HCID 596416776-(2-chlorophenyl)-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one

Product 1

HCID 156035336-(2-chlorophenyl)-7-(4-chlorophenyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-oneYield 84%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

A suspension of 6-(2-chlorophenyl)-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (36 mg, 0.1 mmol), 1,1,1-trifluoro-3-iodopropane (67 mg, 0.3 mmol) and solid K2CO3 (42 mg, 0.3 mmol) in anhydrous DMF (0.6 mL) was stirred at room temperature for 2 h. Analysis by HPLC/MS indicated the reaction was not complete. Additional 1,1,1-trifluoro-3-iodopropane (67 mg, 0.3 mmol) was added, the reaction was allowed to continue at room temperature for 16 h, then at 45° C. for 30 min. After cooling to room temperature, the reaction mixture was partitioned between water and EtOAc. The separated EtOAc layer was washed with water, saturated aqueous NaCl, dried (Na2SO4) and concentrated under reduced pressure. The crude product was purified using a silica gel cartridge (12 g) eluting with a gradient of EtOAc (0-60%) in hexanes to yield a yellow oily product, which was lyophilized in acetonitrile to afford 38 mg (84%) of the title compound as a yellow powder. LC/MS (method A): retention time=3.69 min, (M+H)+=453. 1H NMR (CDCl3, 400 MHz): δ 7.44 (m, 2H), 7.35 (m, 2H), 7.25 (m, 1H), 7.21 (d,J=8.8 Hz, 2H), 7.05 (d,J=8.8 Hz, 2H), 4.36 (m, 2H), 2.76 (m, 2H).

Workup

  1. waitto continue at room temperature for 16 h
  2. waitat 45° C. for 30 min
  3. temperatureAfter cooling to room temperature
  4. customthe reaction mixture was partitioned between water and EtOAc
  5. washThe separated EtOAc layer was washed with water, saturated aqueous NaCl
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified
  9. washeluting with a gradient of EtOAc (0-60%) in hexanes
  10. customto yield a yellow oily product, which

Sources & evidence

ORD record
ord-3c0a9681d9974eb3a191d95dfaed64fc
Source dataset
uspto-grants-2008_01
Patent number
US07317012B2

Reaction notes

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