Potassium Carbonate → 6-[4-Methyl-4-(2-trifluoromethylphenoxy)piperidin-1-YL]pyridazine-3-carboxylic acid (2-cyclopropylethyl)amide

HRID 552167

Reaction equation

HRID 552167 reaction equation
[CH:1]1([CH2:4][CH2:5][NH:6][C:7]([C:9]2[N:10]=[N:11][C:12](Cl)=[CH:13][CH:14]=2)=[O:8])[CH2:3][CH2:2]1.[CH3:16][C:17]1([O:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[C:30]([F:33])([F:32])[F:31])[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH:1]1([CH2:4][CH2:5][NH:6][C:7]([C:9]2[N:10]=[N:11][C:12]([N:20]3[CH2:19][CH2:18][C:17]([CH3:16])([O:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[C:30]([F:31])([F:32])[F:33])[CH2:22][CH2:21]3)=[CH:13][CH:14]=2)=[O:8])[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 655615656-Chloro-N-(2-cyclopropylethyl)pyridazine-3-carboxamideHCID 671715074-Methyl-4-(2-trifluoromethylphenoxy)piperidine

Product 1

HCID 115396356-[4-Methyl-4-(2-trifluoromethylphenoxy)piperidin-1-YL]pyridazine-3-carboxylic acid (2-cyclopropylethyl)amideYield 20%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of 6-chloropyridazine-3-carboxylic acid (2-cyclopropylethyl)amide (0.020 g, 0.090 mmol) in dioxane (5 mL) was added 4-methyl-4-(2-trifluoromethylphenoxy)piperidine (0.015 g, 0.060 mmol), potassium carbonate (0.033 g, 0.240 mmol) and tetrabutyl ammonium bromide (0.002 g, 0.001 mmol). The resulting mixture was stirred at reflux for 48 hours, filtered and then concentrated in vacuo. The crude product was purified by column chromatography to yield the title compound in 20% yield (0.005 g). 1H NMR (300 MHz, CDCl3) δ 8.02-7.96 (m, 2H), 7.60-7.57 (m, 1H), 7.48-7.40 (m, 1H), 7.14-7.12 (d, J=8.0 Hz, 1H), 7.06-6.99 (m, 2H), 4.25-4.21 (m, 2H), 3.65-3.51 (m, 4H), 2.35-2.31 (m, 2H), 1.85-1.74 (m, 2H), 1.53-1.46 (dd, J=6.6 and 7.0 Hz, 2H), 1.20 (s, 3H), 0.77-0.69 (m, 1H), 0.48-0.42 (m, 2H), 0.11-0.05 (m, 2H). MS (ES+) m/z 449.4 (M+1).

Workup

  1. temperatureat reflux for 48 hours
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-ecdf6e9ce59441179dbb6b993c0550da
Source dataset
uspto-grants-2011_05
Patent number
US07951805B2

Linked notes

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