Triethylamine → 6-[4-(4-Fluorobenzoyl)piperidin-1-YL]pyridazine-3-carboxylic acid (2-cyclopropylethyl)amide

HRID 552168

Reaction equation

HRID 552168 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]([C:23]([CH:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)=[O:24])=[CH:19][CH:18]=1.C(N(CC)CC)C>C(#N)C>[CH:1]1([CH2:4][CH2:5][NH:6][C:7]([C:9]2[N:10]=[N:11][C:12]([N:28]3[CH2:29][CH2:30][CH:25]([C:23](=[O:24])[C:20]4[CH:19]=[CH:18][C:17]([F:16])=[CH:22][CH:21]=4)[CH2:26][CH2:27]3)=[CH:13][CH:14]=2)=[O:8])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27244404-(4-Fluorobenzoyl)piperidineHCID 655615656-Chloro-N-(2-cyclopropylethyl)pyridazine-3-carboxamide

Product 1

HCID 116253966-[4-(4-Fluorobenzoyl)piperidin-1-YL]pyridazine-3-carboxylic acid (2-cyclopropylethyl)amideYield 85%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 6-chloropyridazine-3-carboxylic acid (2-cyclopropylethyl)amide (0.500 g, 2.22 mmol), (4-fluorophenyl)piperidin-4-ylmethanone (0.620 g, 2.55 mmol) and triethylamine (0.7 mL, 5 mmol) in acetonitrile (20 mL) was heated to reflux overnight. The solvent was removed in vacuo. The residue was diluted with water, then extracted with ethyl acetate. The residue obtained upon the evaporation of solvent was purified by column chromatography. The title compound was obtained as a white solid in 85% yield (0.270 g). 1H NMR (300 MHz, CDCl3) δ 8.26 (d, J=9.0 Hz, 1H), 8.02-7.93 (m, 2H), 7.65 (d, J=9.0 Hz, 1H), 7.2-7.11 (m, 2H), 6.98 (d, J=9.0 Hz, 1H), 4.55-4.44 (m, 2H), 3.63-3.49 (m, 3H), 3.32-3.19 (m, 2H), 2.5-1.8 (m, 2H), 1.7-1.44 (m, 4H), 0.8-0.67 (m, 1H), 0.52-0.41 (m, 2H), 0.15-0.07 (m, 2H). 13C NMR (75 MHz, CDCl3) δ 200.1, 167.5, 164.1, 163.2, 161.4, 159.9, 158.9, 151.8, 144.6, 132.0, 131.0, 130.9, 129.4, 128.0, 126.9, 116.1, 115.8, 112.2, 44.5, 43.1, 40.0, 39.6, 34.5, 34.3, 27.9, 8.64, 8.6, 4.2. MS (ES+) m/z 397 (M+1).

Workup

  1. temperaturewas heated
  2. temperatureto reflux overnight
  3. customThe solvent was removed in vacuo
  4. additionThe residue was diluted with water
  5. extractionextracted with ethyl acetate
  6. customThe residue obtained upon the evaporation of solvent
  7. customwas purified by column chromatography

Sources & evidence

ORD record
ord-e3bb0416ff3a4852a8a6d7e2bd40bb10
Source dataset
uspto-grants-2011_05
Patent number
US07951805B2

Linked notes

Loading…