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

HRID 1666401Notes

Reaction equation

HRID 1666401 reaction equation
Cl.[CH3:2][C:3]1[C:4]([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:5][CH:6]=[CH: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[C:4]([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:5][CH:6]=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 20150036Phenyl pyridazin-3-ylcarbamateHCID 668760903-Methyl-2-(3-(piperidin-4-ylidenemethyl)phenoxy)pyridine hydrochloride

Product 1

HCID 249644244-(3-(3-methylpyridin-2-yloxy)benzylidene)-N-(pyridazin-3-yl)piperidine-1-carboxamideYield 66.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

3-Methyl-2-(3-(piperidin-4-ylidenemethyl)phenoxy)pyridine hydrochloride (500 mg, 1.42 mmol, from Example 42, Step 5), phenyl pyridazin-3-ylcarbamate (335 mg, 1.56 mmol) and triethylamine (0.79 mL, 5.66 mmol) were combined in acetonitrile (10 mL) and stirred at room temperature. After 16 h, the reaction was concentrated forming a residue 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 (0-5%, (8:1 EtOH:conc. NH4CH):CH2Cl2) to afford the title compound (380 mg) as a white foam. MS (APCI 10V) AP+ 402.0, 281.1; 1H NMR (400 MHz, CD3OD) δ ppm 2.33 (s, 3H) 2.46 (td, J=5.86, 0.80 Hz, 2H) 2.59 (td, J=5.71, 0.82 Hz, 2H) 3.52-3.62 (m, 2H) 3.64-3.71 (m, 2H) 6.44 (s, 1H) 6.84-6.94 (m, 2H) 7.03 (d, J=7.24 Hz, 1H) 7.05 (d, J=7.33 Hz, 1H) 7.34 (dd, J=8.78, 7.66 Hz, 1H) 7.59 (dd, J=9.15, 4.67 Hz, 1H) 7.66-7.73 (m, 1H) 7.87-7.96 (m, J=4.96, 1.22, 0.55, 0.55 Hz, 1H) 8.12 (d, J=8.97 Hz, 1H) 8.78 (d, J=4.26 Hz, 1H).

Workup

  1. concentrationthe reaction was concentrated
  2. customforming a residue
  3. customthe residue was partitioned between EtOAc and water
  4. customThe organic layer was separated
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography (0-5%, (8:1 EtOH:conc. NH4CH):CH2Cl2)

Sources & evidence

ORD record
ord-6c706a13c73343d6a36cebd4dac56402
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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