1-(4-Fluorophenyl)piperazine → 6-[4-(4-Fluorophenyl)piperazin-1-YL]pyridazine-3-carboxylic acid (2-cyclopropylethyl)amide

HRID 913271Notes

Reaction equation

HRID 913271 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.[F:16][C:17]1[CH:22]=[CH:21][C:20]([N:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)=[CH:19][CH:18]=1.N12CCCN=C1CCCCC2>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C>[CH:1]1([CH2:4][CH2:5][NH:6][C:7]([C:9]2[N:10]=[N:11][C:12]([N:26]3[CH2:25][CH2:24][N:23]([C:20]4[CH:19]=[CH:18][C:17]([F:16])=[CH:22][CH:21]=4)[CH2:28][CH2:27]3)=[CH:13][CH:14]=2)=[O:8])[CH2:3][CH2:2]1

Participants

7

Reactant 3

HCID 752601-(4-Fluorophenyl)piperazineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 655615656-Chloro-N-(2-cyclopropylethyl)pyridazine-3-carboxamide

Product 1

HCID 114944146-[4-(4-Fluorophenyl)piperazin-1-YL]pyridazine-3-carboxylic acid (2-cyclopropylethyl)amideYield 74%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 6-chloropyridazine-3-carboxylic acid (2-cyclopropylethyl)amide (0.120 g, 0.532 mmol) in DMF (2.3 mL) was treated with 1-(4-fluorophenyl)piperazine (0.117 g, 0.638 mmol) in the presence of 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) (0.23 mL, 1.54 mmol) and tetra-n-butylammonium iodide (Bu4NI) (11 mg, 0.0298 mmol). The reaction mixture was heated at 75° C. to 80° C. for 15 hours, cooled to room temperature, diluted with ethyl acetate (100 mL). The organic layer was washed with water (3×10 mL), brine (3×10 mL), dried over Na2SO4, and then concentrated in vacuo. The crude product was purified by column chromatography to give the title compound as a white powder in 74% yield (0.146 g). 1H NMR (300 MHz, CDCl3) δ 8.05-7.99 (m, 2H), 7.02-6.89 (m, 5H), 3.90 (t, J=5.2 Hz, 4H), 3.55 (m, 2H), 3.23 (t, J=5.2 Hz, 4H), 1.55-1.47 (m, 2H), 0.79-0.72 (m, 1H), 0.49-0.43 (m, 2H), 0.11-0.06 (m, 2H). MS (ES+) m/z 370.3 (M+1).

Workup

  1. temperatureThe reaction mixture was heated at 75° C. to 80° C. for 15 hours
  2. washThe organic layer was washed with water (3×10 mL), brine (3×10 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-bc33c9611c7441b99b4e3002cdb5bf41
Source dataset
uspto-grants-2011_09
Patent number
US08026360B2

Reaction notes

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