Pyridine → HCID 178474895, compound

HRID 1023858Notes

Reaction equation

HRID 1023858 reaction equation
[NH:1]1[CH:5]=[C:4]([C:6]2[CH:32]=[CH:31][CH:30]=[CH:29][C:7]=2[O:8][CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:27])[CH:19]([NH2:26])[CH:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[CH:13][C:12]=2[Cl:28])[N:3]=[CH:2]1.N1C=CC=CC=1.[C:39](Cl)(=[O:41])[CH3:40]>ClCCl>[NH:1]1[CH:5]=[C:4]([C:6]2[CH:32]=[CH:31][CH:30]=[CH:29][C:7]=2[O:8][CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:27])[CH:19]([NH:26][C:39](=[O:41])[CH3:40])[CH:20]3[CH2:21][CH2:22][O:23][CH2:24][CH2:25]3)=[CH:13][C:12]=2[Cl:28])[N:3]=[CH:2]1

Participants

5

Reactant 3

HCID 1049PyridineHCID 6367Acetyl chlorideHCID 178511434HCID 178511434, compound

Product 1

HCID 178474895HCID 178474895, compoundYield 61.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N-(4-(2-(2-(1H-imidazol-4-yl)phenoxy)ethyl)-3-chlorophenyl)-2-amino-2-(tetrahydro-2H-pyran-4-yl)acetamide (40 mg, 0.088 mmol) in dichloromethane (3 mL) was added pyridine (29 μL, 0.352 mmol) and acetyl chloride (29 μL, 0.264 mmol). The reaction was stirred at room temperature for 16 h. The solvent was removed under reduced pressure. The crude product was dissolved in methanol (4 mL) and refluxed for 2 h. The solution was concentrated and the residue was purified by flash column chromatography (silica gel, 5%-10% MeOH/DCM as eluent) to afford the desired product as a white solid (27 mg, 0.054 mmol, 61%). 1H NMR: 1.42-1.58 (m, 3H), 1.68 (d, 1H, J=12.8 Hz), 2.03-2.07 (m, 1H), 2.08 (s, 3H), 3.24-3.31 (m, 4H), 3.94 (t, 2H, J=11.2 Hz), 4.39 (t, 2H, J=6 Hz), 4.61 (t, 1H, J=8.4 Hz), 6.81 (d, 1H, J=8.4 Hz), 6.99 (d, 2H, J=8 Hz), 7.18-7.24 (m, 3H), 7.37 (dd, 1H, J=8 Hz, 1.6 Hz), 7.60 (s, 1H), 7.77 (s, 1H),

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionThe crude product was dissolved in methanol (4 mL)
  3. temperaturerefluxed for 2 h
  4. concentrationThe solution was concentrated
  5. customthe residue was purified by flash column chromatography (silica gel, 5%-10% MeOH/DCM as eluent)

Sources & evidence

ORD record
ord-e6008e9128634557a952df6e2a76139d
Source dataset
uspto-grants-2014_05
Patent number
US08722720B2

Reaction notes

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