Cyclohexanol → 6-(2-Chlorophenyl)-7-(4-chlorophenyl)-3-(cyclohexyloxy)-[1,2,4]triazolo[4,3-b]pyridazine

HRID 1867873Notes

Reaction equation

HRID 1867873 reaction equation
[CH:1]1([OH:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Na].Cl[C:10]1[N:14]2[N:15]=[C:16]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[Cl:32])[C:17]([C:19]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=3)=[CH:18][C:13]2=[N:12][N:11]=1>C1COCC1>[Cl:32][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=1[C:16]1[C:17]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)=[CH:18][C:13]2[N:14]([C:10]([O:7][CH:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)=[N:11][N:12]=2)[N:15]=1

Participants

5

Reactant 3

HCID 7966CyclohexanolHCID 5360545SodiumHCID 579797573-Chloro-6-(2-chlorophenyl)-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazine

Product 1

HCID 119930186-(2-Chlorophenyl)-7-(4-chlorophenyl)-3-(cyclohexyloxy)-[1,2,4]triazolo[4,3-b]pyridazineYield 7.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of cyclohexanol (0.5 g, 5 mmol) in anhydrous THF (1 mL) at room temperature was added freshly cut sodium metal (35 mg, 1.5 mmol). The reaction mixture was stirred at room temperature for 20 min, then at 60° C. for 30 min, and then allowed to cool to room temperature. Into this mixture was added 3-chloro-6-(2-chlorophenyl)-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazine (115 mg, 0.3 mmol), the resulting mixture was stirred at room temperature under argon for 16 h. The reaction was carefully quenched by addition of methanol, then diluted with EtOAc. The solution was washed with H2O, saturated aqueous NaCl, dried (Na2SO4), filtered and concentrated. The obtained residue was purified using a silica gel cartridge (12 g) eluting with a gradient of EtOAc (0-40%) in hexanes to afford 10 mg (7.6%) of the title compound as a pale-yellow solid. HPLC/MS (method A): retention time=4.06 min, (M+H)+=439.1. 1H NMR (CDCl3, 400 MHz): δ 7.84 (s, 1H), 7.46 (dd, J=5.62, 3.67 Hz, 1H), 7.32-7.37 (m, 2H), 7.25-7.30 (m, 1H), 7.20 (d, J=8.56 Hz, 2H), 7.03-7.08 (m, 2H), 5.21-5.29 (m, 1H), 2.28 (d, J=12.96 Hz, 2H), 1.88 (d, J=4.40 Hz, 2H), 1.60-1.80 (m, 3H), 1.45-1.52 (m, 2H), 1.20-1.40(m, 1H).

Workup

  1. waitat 60° C. for 30 min
  2. temperatureto cool to room temperature
  3. stirringthe resulting mixture was stirred at room temperature under argon for 16 h
  4. customThe reaction was carefully quenched by addition of methanol
  5. additiondiluted with EtOAc
  6. washThe solution was washed with H2O, saturated aqueous NaCl
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe obtained residue was purified
  11. washeluting with a gradient of EtOAc (0-40%) in hexanes

Sources & evidence

ORD record
ord-430638d8d44b4a0086789165a1a62754
Source dataset
uspto-grants-2009_12
Patent number
US07632837B2

Reaction notes

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