Triethylamine → 4-(3-(5-methylpyridin-2-yloxy)benzylidene)-N-(pyridazin-3-yl)piperidine-1-carboxamide

HRID 1666407Notes

Reaction equation

HRID 1666407 reaction equation
Cl.[CH3:2][C:3]1[CH:4]=[CH:5][C:6]([O:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([CH:16]=[C:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)[CH:11]=2)=[N:7][CH:8]=1.[N:23]1[CH:28]=[CH:27][CH:26]=[C:25]([NH:29][C:30](=O)[O:31]C2C=CC=CC=2)[N:24]=1.C(N(CC)CC)C>C(#N)C>[CH3:2][C:3]1[CH:4]=[CH:5][C:6]([O:9][C:10]2[CH:11]=[C:12]([CH:13]=[CH:14][CH:15]=2)[CH:16]=[C:17]2[CH2:22][CH2:21][N:20]([C:30]([NH:29][C:25]3[N:24]=[N:23][CH:28]=[CH:27][CH:26]=3)=[O:31])[CH2:19][CH2:18]2)=[N:7][CH:8]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 20150036Phenyl pyridazin-3-ylcarbamateHCID 668761665-Methyl-2-(3-(piperidin-4-ylidenemethyl)phenoxy)pyridine hydrochloride

Product 1

HCID 249644264-(3-(5-methylpyridin-2-yloxy)benzylidene)-N-(pyridazin-3-yl)piperidine-1-carboxamideYield 81.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

5-Methyl-2-(3-(piperidin-4-ylidenemethyl)phenoxy)pyridine hydrochloride (507 mg, 1.6 mmol, from Example 44, Step 5), phenyl pyridazin-3-ylcarbamate (430 mg, 2.0 mmol) and triethylamine (0.892 mL, 6.4 mmol) were combined in acetonitrile (10 mL) and stirred at room temperature. After 16 h, the reaction was concentrated and the residue was partitioned between EtOAc and water. The organic layer was separated, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (0-10%, MeOH:CH2Cl2) to afford the title compound (526 mg) as a foamy white solid. MS APCI M+ 402.1, 281.2 M− 400.1; 1H NMR (400 MHz, CD3OD) δ ppm 2.29 (s, 3H) 2.46 (td, J=5.71, 0.93 Hz, 2H) 2.58 (td, J=5.74, 1.06 Hz, 2H) 3.52-3.61 (m, 2H) 3.65-3.71 (m, 2H) 6.44 (s, 1H) 6.85 (dd, J=8.41, 0.33 Hz, 1H) 6.89-6.96 (m, J=4.21, 4.21, 2.47, 1.01 Hz, 2H) 7.04-7.11 (m, J=7.63, 1.41, 1.04, 0.83 Hz, 1H) 7.31-7.42 (m, 1H) 7.59 (dd, J=9.09, 4.70 Hz, 1H) 7.66 (ddd, J=8.39, 2.49, 0.66 Hz, 1H) 7.97 (td, J=1.63, 0.77 Hz, 1H) 8.12 (d, J=9.32 Hz, 1H) 8.79 (d, J=4.37 Hz, 1H).

Workup

  1. concentrationthe reaction was concentrated
  2. customthe residue was partitioned between EtOAc and water
  3. customThe organic layer was separated
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography (0-10%, MeOH:CH2Cl2)

Sources & evidence

ORD record
ord-8558b4454d90476ab418e75e7f0d9982
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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