Triethylamine → 4-(3-(6-methylpyridin-2-yloxy)benzylidene)-N-(pyridin-3-yl)piperidine-1-carboxamide

HRID 1666393Notes

Reaction equation

HRID 1666393 reaction equation
Cl.[CH3:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([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:4]=1.[N:23]1[CH:28]=[CH:27][CH:26]=[C:25]([NH:29][C:30](=O)[O:31]C2C=CC=CC=2)[CH:24]=1.C(N(CC)CC)C>C(#N)C>[CH3:2][C:3]1[N:4]=[C:5]([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[CH:24]=[N:23][CH:28]=[CH:27][CH:26]=3)=[O:31])[CH2:19][CH2:18]2)[CH:6]=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 6935890Phenyl pyridin-3-ylcarbamateHCID 668757912-Methyl-6-(3-(piperidin-4-ylidenemethyl)phenoxy)pyridine hydrochloride

Product 1

HCID 249640614-(3-(6-methylpyridin-2-yloxy)benzylidene)-N-(pyridin-3-yl)piperidine-1-carboxamideYield 70.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

2-Methyl-6-(3-(piperidin-4-ylidenemethyl)phenoxy)pyridine hydrochloride (500 mg, 1.42 mmol, from Step 5), phenyl pyridin-3-ylcarbamate (333 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. NH4OH):CH2Cl2) to afford the title compound (399 mg) as a foamy white solid. MS (APCI 10V) AP+ 401.5, 281.2 1H NMR (400 MHz, CD3OD) d ppm 2.42 (s, 3H) 2.45 (td, J=5.74, 1.04 Hz, 2H) 2.56 (td, J=5.80, 1.15 Hz, 2H) 3.51-3.58 (m, 2H) 3.61-3.67 (m, 2H) 6.44 (s, 1H) 6.64 (d, J=8.24 Hz, 1H) 6.91-6.97 (m, 2H) 6.99 (d, J=7.19 Hz, 1H) 7.07 (d, J=7.65 Hz, 1H) 7.29-7.40 (m, 2H) 7.63-7.74 (m, 1H) 7.90 (ddd, J=8.38, 2.53, 1.39 Hz, 1H) 8.16 (dd, J=4.79, 1.40 Hz, 1H) 8.58 (d, J=2.31 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. NH4OH):CH2Cl2)

Sources & evidence

ORD record
ord-ab7055ae372b4a928d82bb4d782a03ec
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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