Cyclohexyl bromide → 6-(2-chlorophenyl)-7-(4-chlorophenyl)-2-cyclohexyl-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one

HRID 2250348Notes

Reaction equation

HRID 2250348 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.Br[CH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1.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]([CH:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)[N:16]=2)[N:13]=1

Participants

6

Reactant 3

HCID 7960Cyclohexyl bromide2×HCID 11430Potassium CarbonateHCID 596416776-(2-chlorophenyl)-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one

Product 1

HCID 156035316-(2-chlorophenyl)-7-(4-chlorophenyl)-2-cyclohexyl-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-oneYield 34.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

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), bromocyclohexane (40 μL, 0.3 mmol) and solid K2CO3 (42 mg, 0.3 mmol) in anhydrous DMF (1 mL) was stirred at 75° C. for 17 h. Analysis by HPLC/MS indicated the reaction was not complete. Additional bromocyclohexane (50 μL, 0.375 mmol) was added, the reaction was allowed to continue at 75° C. for 24 h more. After cooling to room temperature, the reaction mixture was partitioned between water (20 mL) and EtOAc (20 mL). The separated EtOAc layer was washed with 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 glassy product, which was lyophilized in acetonitrile to afford 15 mg (34%) of the title compound as a yellow powder. LC/MS (method A): retention time=4.06 min, (M+H)+=439. 1H NMR (CDCl3, 400 MHz): δ 7.18-7.50 (m, 5H), 7.19 (d,J=8.8 Hz, 2H), 7.03 (d,J=8.8 Hz, 2H), 4.47 (m, 1H), 1.26-2.04 (m, 10H).

Workup

  1. waitto continue at 75° C. for 24 h
  2. temperatureAfter cooling to room temperature
  3. customthe reaction mixture was partitioned between water (20 mL) and EtOAc (20 mL)
  4. washThe separated EtOAc layer was washed with 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 glassy product, which

Sources & evidence

ORD record
ord-136e541f3274442e8f3bd557825b3bc1
Source dataset
uspto-grants-2008_01
Patent number
US07317012B2

Reaction notes

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