Piperidine → 6-(2-Chlorophenyl)-7-(4-chlorophenyl)-3-(piperidin-1-yl)-[1,2,4]triazolo [4,3-b]pyridazine

HRID 1867870Notes

Reaction equation

HRID 1867870 reaction equation
Cl[C:2]1[N:6]2[N:7]=[C:8]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[Cl:24])[C:9]([C:11]3[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=3)=[CH:10][C:5]2=[N:4][N:3]=1.[NH:25]1[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1>>[Cl:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[C:8]1[C:9]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)=[CH:10][C:5]2[N:6]([C:2]([N:25]3[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]3)=[N:3][N:4]=2)[N:7]=1

Participants

3

Reactant 2

HCID 8082PiperidineHCID 579797573-Chloro-6-(2-chlorophenyl)-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazine

Product 1

HCID 119930156-(2-Chlorophenyl)-7-(4-chlorophenyl)-3-(piperidin-1-yl)-[1,2,4]triazolo [4,3-b]pyridazineYield 48%

Conditions

Temperature
100 °C

Procedure

A suspension of 3-chloro-6-(2-chlorophenyl)-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazine (22 mg, 0.06 mmol) in piperidine (0.5 mL) was stirred at 100° C. for 16 h. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The crude product was purified using reverse phase preparative HPLC (Conditions: Phenomenex Luna 5μ C18 21.2×100 mm; Eluted with 60% to 100% B, 8 min gradient, 100% B hold for 7 min, (A=90% H2O, 10% MeOH, 0.1% trifluoroacetic acid and B=10% H2O, 90% MeOH, 0.1% trifluoroacetic acid); Flow rate at 20 mL/min, UV detection at 220 nm). The desired fractions were concentrated under reduced pressure. The residue was dissolved in EtOAc, washed with saturated aqueous NaHCO3, water, saturated aqueous NaCl, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was lyophilized in acetonitrile to afford 12 mg (48%) of the title compound as a yellow powder. HPLC/MS (method A): retention time=3.82 min, (M+H)+=424.1. 1H NMR (CDCl3, 400 MHz): δ 7.92 (s, 1H), 7.29-7.39 (m, 4H), 7.21 (d, J=8.56 Hz, 2H), 7.04 (d, J=8.56 Hz, 2H), 3.66 (s, 4H), 1.72-1.81 (m, 4H), 1.69 (d, J=4.89 Hz, 2H).

Workup

  1. temperatureAfter cooling to room temperature
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. customThe crude product was purified
  4. washEluted with 60% to 100% B, 8 min gradient, 100% B hold for 7 min
  5. concentrationThe desired fractions were concentrated under reduced pressure
  6. dissolutionThe residue was dissolved in EtOAc
  7. washwashed with saturated aqueous NaHCO3, water, saturated aqueous NaCl
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ecd5f63ca3f24a959d4029bf72ebc07f
Source dataset
uspto-grants-2009_12
Patent number
US07632837B2

Reaction notes

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