Isopropyl iodide → 5-(3,4-Dimethoxyphenyl)-4,4-dimethyl-2-(1-{[2-methyl-5-(propan-2-yloxy)phenyl]carbonyl}piperidin-4-yl)-2,4-dihydro-3H-pyrazol-3-one

HRID 524216Notes

Reaction equation

HRID 524216 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[C:12]([CH3:34])([CH3:33])[C:13](=[O:32])[N:14]([CH:16]3[CH2:21][CH2:20][N:19]([C:22]([C:24]4[CH:29]=[C:28]([OH:30])[CH:27]=[CH:26][C:25]=4[CH3:31])=[O:23])[CH2:18][CH2:17]3)[N:15]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].C(=O)([O-])[O-].[K+].[K+].I[CH:42]([CH3:44])[CH3:43]>C(#N)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[C:12]([CH3:34])([CH3:33])[C:13](=[O:32])[N:14]([CH:16]3[CH2:21][CH2:20][N:19]([C:22]([C:24]4[CH:29]=[C:28]([O:30][CH:42]([CH3:44])[CH3:43])[CH:27]=[CH:26][C:25]=4[CH3:31])=[O:23])[CH2:18][CH2:17]3)[N:15]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

5

Reactant 3

HCID 6362Isopropyl iodideHCID 11430Potassium CarbonateHCID 462020675-(3,4-Dimethoxyphenyl)-2-{1-[(5-hydroxy-2-methylphenyl)carbonyl]piperidin-4-yl}-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one

Product 1

HCID 462020695-(3,4-Dimethoxyphenyl)-4,4-dimethyl-2-(1-{[2-methyl-5-(propan-2-yloxy)phenyl]carbonyl}piperidin-4-yl)-2,4-dihydro-3H-pyrazol-3-one

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

0.28 g of 5-(3,4-dimethoxyphenyl)-2-{1-[(5-hydroxy-2-methylphenyl)carbonyl]piperidin-4-yl}-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one (compound described in example 85) and 0.25 g potassium carbonate are suspended in 5 ml of acetonitrile. 0.31 g of 2-iodopropane is added and the reaction mixture is heated to reflux under a blanket of nitrogen for about 16 h until the reaction is completed according to TLC analysis. The solvent is evaporated under reduced pressure, and the remaining residue is taken up in EA. The organic phase is washed with water, twice with 1 M aqueous sodium hydroxide solution and with brine, dried over MgSO4, and the solvent is removed under reduced pressure. Purification of the resulting crude product by crystallization from diethyl ether yields the title compound.

Workup

  1. temperaturethe reaction mixture is heated
  2. temperatureto reflux under a blanket of nitrogen for about 16 h until the reaction
  3. customThe solvent is evaporated under reduced pressure
  4. washThe organic phase is washed with water, twice with 1 M aqueous sodium hydroxide solution and with brine
  5. dry with materialdried over MgSO4
  6. customthe solvent is removed under reduced pressure
  7. customPurification of the resulting crude product
  8. customby crystallization from diethyl ether

Sources & evidence

ORD record
ord-8b450e81baf64ea0b9b63e40bc250470
Source dataset
uspto-grants-2016_05
Patent number
US09340522B2

Reaction notes

Loading…