Potassium Carbonate → [1-[2-[3-(3,4-Dichlorophenyl)-1-(3,4,5-trimethoxybenzoyl)pyrrolidin-3-yl]ethyl]piperidin-4-yl]-[1-(pyridin-2-ylmethyl)benzimidazol-2-yl]methanone

HRID 2269860Notes

Reaction equation

HRID 2269860 reaction equation
CS(O)(=O)=[O:3].[CH3:6][O:7][C:8]1[CH:9]=[C:10]([CH:45]=[C:46]([O:50][CH3:51])[C:47]=1[O:48][CH3:49])[C:11]([N:13]1[CH2:17][CH2:16][C:15]([CH2:26][CH2:27][N:28]2[CH2:33][CH2:32][CH:31]([C:34]([C:36]3[NH:40][C:39]4[CH:41]=[CH:42][CH:43]=[CH:44][C:38]=4[N:37]=3)=[O:35])[CH2:30][CH2:29]2)([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=2)[CH2:14]1)=[O:12].Cl.[Cl:53][CH2:54][C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][N:56]=1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O.O>[Cl:53][CH2:20][Cl:25].[CH3:6][OH:7].[OH-:3].[NH4+:13].[CH3:6][O:7][C:8]1[CH:9]=[C:10]([CH:45]=[C:46]([O:50][CH3:51])[C:47]=1[O:48][CH3:49])[C:11]([N:13]1[CH2:17][CH2:16][C:15]([CH2:26][CH2:27][N:28]2[CH2:29][CH2:30][CH:31]([C:34]([C:36]3[N:37]([CH2:54][C:55]4[CH:60]=[CH:59][CH:58]=[CH:57][N:56]=4)[C:38]4[CH:44]=[CH:43][CH:42]=[CH:41][C:39]=4[N:40]=3)=[O:35])[CH2:32][CH2:33]2)([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=2)[CH2:14]1)=[O:12]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 23392Picolyl chloride hydrochlorideHCID 867576761-(3,4,5-trimethoxy-benzoyl)-3-[2-[4-[1 H-benzoimidazole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(3,4-dichloro-phenyl)-pyrrolidine methanesulfonate salt

Product 2

HCID 10147107[1-[2-[3-(3,4-Dichlorophenyl)-1-(3,4,5-trimethoxybenzoyl)pyrrolidin-3-yl]ethyl]piperidin-4-yl]-[1-(pyridin-2-ylmethyl)benzimidazol-2-yl]methanoneHCID 21896990Dichloromethane methanol ammonium hydroxide

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

Combine 1-(3,4,5-trimethoxy-benzoyl)-3-[2-[4-[1 H-benzoimidazole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(3,4-dichloro-phenyl)-pyrrolidine methanesulfonate salt (0.60 g, 0.70 mmol) and 2-(chloromethyl)pyridine hydrochloride (0.46 g, 2.8 mmol), and potassium carbonate (1.14 g, 8.25 mmol) in acetone (12 mL) and water (4 mL). Heat to reflux. After 24 hours, cool to ambient temperature and concentrate the reaction mixture in vacuo and dilute with ethyl acetate. Extract with water, saturated aqueous sodium bicarbonate solution, and saturated aqueous sodium chloride solution. Dry the organic layer over MgSO4, filter, and concentrate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 10/1/0.1 dichloromethane/methanol/ammonium hydroxide to give the title compound: Rf=0.58 (silica gel, 10/1/0.1 dichloromethane/methanol/ammonium hydroxide).

Workup

  1. temperatureHeat to reflux
  2. concentrationconcentrate the reaction mixture in vacuo
  3. additiondilute with ethyl acetate
  4. extractionExtract with water, saturated aqueous sodium bicarbonate solution, and saturated aqueous sodium chloride solution
  5. dry with materialDry the organic layer over MgSO4
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. customto give a residue

Sources & evidence

ORD record
ord-464f05cb9c6548b8a11ca1676dc801f2
Source dataset
uspto-grants-2001_12
Patent number
US06329392B1

Reaction notes

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