Triethylamine → HCID 67012081, compound

HRID 2354753Notes

Reaction equation

HRID 2354753 reaction equation
[NH2:1][C:2]1[N:7]=[N:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:22]([F:25])([F:24])[F:23])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Cl[C:27]([O:29][C:30](Cl)(Cl)Cl)=[O:28].[CH3:34][C:35]([CH3:40])([CH3:39])[CH2:36]CO.C(N(CC)CC)C>O1CCOCC1>[CH3:34][C:35]([CH3:40])([CH3:39])[CH2:36][CH2:30][O:29][C:27](=[O:28])[NH:1][C:2]1[N:7]=[N:6][C:5]([N:8]2[CH2:9][CH2:10][N:11]([C:14](=[O:15])[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:22]([F:25])([F:24])[F:23])[CH2:12][CH2:13]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10426DiphosgeneHCID 122333,3-Dimethyl-1-butanolHCID 66849536[4-(6-Aminopyridazin-3-yl)piperazin-1-yl](2-trifluoromethylphenyl)methanone

Product 1

HCID 67012081HCID 67012081, compoundYield 11%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of [4-(6-aminopyridazin-3-yl)piperazin-1-yl](2-trifluoromethyl-phenyl)methanone (200 mg, 0.57 mmol) in 10 mL of dioxane was added trichloromethyl chloroformate (112.7 mg, 0.57 mmol) and stirred at ambient temperature. After 30 minutes 3,3-dimethylbutan-1-ol (175.5 mg, 1.71 mmol) and triethylamine (57.6 mg, 0.57 mmol) were added and the temperature was raised to 80° C. The mixture was stirred for 3 h under N2, and then concentrated. The residue was dissolved in dichloromethane (100 mL), and washed with 1 N HCl (2×20 mL), saturated NaHCO3 (2×20 mL) and finally with brine (2×20 mL). The combined organic extract was dried over anhydrous Na2SO4, concentrated, and then purified by column chromatography eluted with hexane:ethyl acetate (1:2). The product was obtained as a white solid (30 mg, 11% yield). 1H NMR (300 MHz, DMSO-d6) δ 10.38, 7.89, 7.83, 7.77, 7.67, 7.54, 7.47, 4.14, 3.10-3.90, 1.55, 0.95.

Workup

  1. temperaturethe temperature was raised to 80° C
  2. stirringThe mixture was stirred for 3 h under N2
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in dichloromethane (100 mL)
  5. washwashed with 1 N HCl (2×20 mL), saturated NaHCO3 (2×20 mL) and finally with brine (2×20 mL)
  6. extractionThe combined organic extract
  7. dry with materialwas dried over anhydrous Na2SO4
  8. concentrationconcentrated
  9. custompurified by column chromatography
  10. washeluted with hexane:ethyl acetate (1:2)

Sources & evidence

ORD record
ord-1d36ae752a4f4a3e8c1bb64e610f1e02
Source dataset
uspto-grants-2010_07
Patent number
US07754711B2

Reaction notes

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