Triethylamine → HCID 69425420, compound

HRID 1766986Notes

Reaction equation

HRID 1766986 reaction equation
[Cl:1][C:2]1[N:7]=[N:6][CH:5]=[C:4]2[N:8]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=3)[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:17])=[N:10][C:3]=12.[CH:25]([NH:28][C:29]1([C:35]([NH2:37])=[O:36])[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1)([CH3:27])[CH3:26].CCN(CC)CC>CCO>[ClH:1].[Cl:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[C:9]1[N:8]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)[C:4]2=[CH:5][N:6]=[N:7][C:2]([N:32]3[CH2:31][CH2:30][C:29]([NH:28][CH:25]([CH3:27])[CH3:26])([C:35]([NH2:37])=[O:36])[CH2:34][CH2:33]3)=[C:3]2[N:10]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 967164-(Isopropylamino)piperidine-4-carboxamideHCID 21113078HCID 21113078, compound

Product 1

HCID 69425420HCID 69425420, compoundYield 44.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 4-chloro-2-(2-chloro-phenyl)-1-(4-chloro-phenyl)-1H-imidazo[4,5-d]pyridazine (I-2h, 11 mg, 0.29 mmol), 4-isopropylamino-piperidine-4-carboxylic acid amide (6 mg, 0.032 mmol) and NEt3 (8 μl, 0.06 mmol) in EtOH (1 ml) was heated under reflux for 2 hours. The reaction mixture was cooled to room temperature and concentrated in vacuo. The residue was diluted with ethylene glycol (1.5 ml) and NEt3 (8 μl) was added. The reaction mixture was heated at 120° C. for 1.5 hours and at 100° C. for 18 hours. The reaction mixture was cooled to room temperature and diluted with H2O. The aqueous solution was extracted with CH2Cl2 (3×) and the combined organic extracts were washed with sat'd aq NaCl, dried, and concentrated in vacuo. The residue was purified on a chromatotron plate (1 mm) using 10:1 CH2Cl2/MeOH(NH3) to give the free amine 2A-1 (8 mg) as a solid: +APCI MS (M+1) 523.9; 1H NMR (CD3OD) δ1.08 (6H, d), 1.80–1.87 (2H, m), 2.16–2.25 (2H, m), 2.95–3.08 (1H, m), 4.18–4.30 (2H, m), 4.32–4.42 (2H, m), 7.30–7.70 (8H, m).

Workup

  1. temperatureunder reflux for 2 hours
  2. concentrationconcentrated in vacuo
  3. additionThe residue was diluted with ethylene glycol (1.5 ml) and NEt3 (8 μl)
  4. additionwas added
  5. temperatureThe reaction mixture was heated at 120° C. for 1.5 hours and at 100° C. for 18 hours
  6. temperatureThe reaction mixture was cooled to room temperature
  7. additiondiluted with H2O
  8. extractionThe aqueous solution was extracted with CH2Cl2 (3×)
  9. washthe combined organic extracts were washed with sat'd aq NaCl
  10. customdried
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified on a chromatotron plate (1 mm)

Sources & evidence

ORD record
ord-09cd2187412d4c028e10f8fa09172a25
Source dataset
uspto-grants-2007_06
Patent number
US07232823B2

Reaction notes

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