Ethyl Methanesulfonate → 4-[(5-Chloro-2-pyridinyl)methoxy]-1-(4-{[(3R)-1-ethyl-3-pyrrolidinyl]-oxy}phenyl)-1H-pyridin-2-one

HRID 15081

Reaction equation

HRID 15081 reaction equation
CS(OCC)(=O)=O.C(#N)C.[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([CH2:18][O:19][C:20]2[CH:25]=[CH:24][N:23]([C:26]3[CH:31]=[CH:30][C:29]([O:32][C@@H:33]4[CH2:37][CH2:36][N:35]([CH:38](C)[CH3:39])[CH2:34]4)=[CH:28][CH:27]=3)[C:22](=[O:41])[CH:21]=2)=[N:16][CH:17]=1>C(Cl)(Cl)Cl>[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([CH2:18][O:19][C:20]2[CH:25]=[CH:24][N:23]([C:26]3[CH:27]=[CH:28][C:29]([O:32][C@@H:33]4[CH2:37][CH2:36][N:35]([CH2:38][CH3:39])[CH2:34]4)=[CH:30][CH:31]=3)[C:22](=[O:41])[CH:21]=2)=[N:16][CH:17]=1

Participants

5

Reactant 3

HCID 6113Ethyl Methanesulfonate2×HCID 6342AcetonitrileHCID 116119264-[(5-Chloro-2-pyridinyl)methoxy]-1-(4-{[(3R)-1-isopropyl-3-pyrrolidinyl]-oxy}phenyl)-1H-pyridin-2-one

Product 1

HCID 115319734-[(5-Chloro-2-pyridinyl)methoxy]-1-(4-{[(3R)-1-ethyl-3-pyrrolidinyl]-oxy}phenyl)-1H-pyridin-2-oneYield 41.3%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
80 °C

Procedure

Ethyl methanesulfonate (0.45 mL) was added to acetonitrile solution of 4-[(5-chloro-2-pyridinyl)methoxy]-1-(4-{[(3R)-3-pyrrolidinyl]oxy}phenyl)-1H-pyridin-2-one (1.65 g, Example 122), and stirred at 80° C. for 2 hours. Additional ethyl methanesulfonate (0.45 mL) was added and stirred at 80° C. for further 2 hours, followed by cooling to room temperature. Chloroform was added to the reaction liquid which then was washed with saturated aqueous sodium hydrogencarbonate solution and saturated brine, and dried over anhydrous potassium carbonate. Concentrating the solvent under reduced pressure, the residue was purified on silica gel column chromatography (C-300; methanol:chloroform=1:100-1:10-1:4). The residue was crystallized from mixed solvent of ethyl acetate and heptane to provide the title compound (660 mg).

Workup

  1. stirringstirred at 80° C. for further 2 hours
  2. temperatureby cooling to room temperature
  3. washthen was washed with saturated aqueous sodium hydrogencarbonate solution and saturated brine
  4. dry with materialdried over anhydrous potassium carbonate
  5. concentrationConcentrating the solvent under reduced pressure
  6. customthe residue was purified on silica gel column chromatography (C-300; methanol:chloroform=1:100-1:10-1:4)
  7. customThe residue was crystallized
  8. additionfrom mixed solvent of ethyl acetate and heptane

Sources & evidence

ORD record
ord-01d3e5beed11407cab04b5788599f5fc
Source dataset
uspto-grants-2010_06
Patent number
US07732456B2

Linked notes

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