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

HRID 2250350Notes

Reaction equation

HRID 2250350 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:32])([F:31])[CH2:27][CH2:28][CH2:29]I.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O.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]([CH2:29][CH2:28][CH2:27][C:26]([F:32])([F:31])[F:25])[N:16]=2)[N:13]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27751891,1,1-Trifluoro-4-iodobutane2×HCID 596416776-(2-chlorophenyl)-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one

Product 1

HCID 156035346-(2-chlorophenyl)-7-(4-chlorophenyl)-2-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-oneYield 73%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of 6-(2-chlorophenyl)-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (20 mg, 0.056 mmol), 1,1,1-trifluoro-4-iodobutane (20 mg, 0.084 mmol) and solid K2CO3 (12 mg, 0.084 mmol) in anhydrous DMF (0.6 mL) was stirred at 80° C. for 1 h. Analysis by HPLC/MS indicated the reaction was not complete. Additional 1,1,1-trifluoro-4-iodobutane (12 mg, 0.084 mmol) was added, the reaction was allowed to continue at 80° C. for 30 min. After cooling to room temperature, the reaction mixture was diluted with water, and extracted with EtOAc (20 mL×2). The combined EtOAc extracts were 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 19 mg (73%) of the title compound as a yellow powder. HPLC (method B): retention time=7.70 min. 1H NMR (CDCl3, 400 MHz): δ 7.45 (m, 2H), 7.35 (m, 2H), 7.25 (m, 1H), 7.20 (d,J=8.8 Hz, 2H), 7.04 (d,j=8.8 Hz, 2H), 4.17 (t,J=6.1 Hz, 2H), 2.17-2.25 (m, 4H).

Workup

  1. waitto continue at 80° C. for 30 min
  2. temperatureAfter cooling to room temperature
  3. extractionextracted with EtOAc (20 mL×2)
  4. washThe combined EtOAc extracts were washed with water, saturated aqueous NaCl
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified
  8. washeluting with a gradient of EtOAc (0-60%) in hexanes
  9. customto yield a yellow oily product, which

Sources & evidence

ORD record
ord-eeb2ed5658d94b52992370242768a3d9
Source dataset
uspto-grants-2008_01
Patent number
US07317012B2

Reaction notes

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