Ethyl Acetate → 1-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1-(4-fluorobenzyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-phenylpyrrolidine

HRID 323211

Reaction equation

HRID 323211 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:26]=[C:27]([O:31][CH3:32])[C:28]=1[O:29][CH3:30])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([CH2:13][CH2:14]OS(C)(=O)=O)[CH2:9]1)=[O:7].[F:33][C:34]1[CH:56]=[CH:55][C:37]([CH2:38][N:39]2[C:43]3[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=3[N:41]=[C:40]2[NH:48][CH:49]2[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]2)=[CH:36][CH:35]=1.C(N(CC)C(C)C)(C)C.C(OCC)(=O)C>C(#N)C.CO.C(OCC)(=O)C>[CH3:32][O:31][C:27]1[CH:26]=[C:5]([CH:4]=[C:3]([O:2][CH3:1])[C:28]=1[O:29][CH3:30])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:13][CH2:14][N:52]2[CH2:53][CH2:54][CH:49]([NH:48][C:40]3[N:39]([CH2:38][C:37]4[CH:55]=[CH:56][C:34]([F:33])=[CH:35][CH:36]=4)[C:43]4[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=4[N:41]=3)[CH2:50][CH2:51]2)([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:9]1)=[O:7]

Participants

7

Reactant 4

HCID 8857Ethyl Acetate2×HCID 81531DiisopropylethylamineHCID 123618TecastemizoleHCID 184646303,4,5-Trimethoxybenzoyl-3-phenyl-3-(2-methanesulfonyloxyethyl)pyrrolidine

Product 1

HCID 98748221-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1-(4-fluorobenzyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-phenylpyrrolidine

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 21584119Ethylacetate methanolSolvent

Procedure

Combine 1-(3,4,5-trimethoxybenzoyl)-3-phenyl-3-(2-methanesulfonyloxyethyl)pyrrolidine (0.42 g, 0.9 mmol) and (1(4-fluorobenzyl)-1H-benzimidazol-2-yl)(piperidin-4-yl)amine (0.49 g, 1.5 mmol), and N,N-diisopropylethylamine (0.40 mL, 2.3 mmol) in acetonitrile (12 mL). Heat to reflux. After 18 hours, pour the reaction mixture into ethyl acetate. Extract twice with water, saturated aqueous sodium bicarbonate solution, and aqueous sodium chloride solution. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Chromatograph the residue on a short column of silica gel eluting sequentially with ethyl acetate and then 25% methanol/ethyl acetate. Evaporate the product containing fractions and partition between dichloromethane and 1/1 brine/water. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to give the title compound: Rf=0.38 silica gel, 25% methanol/ethyl acetate).

Workup

  1. temperatureHeat to reflux
  2. extractionExtract twice with water, saturated aqueous sodium bicarbonate solution, and aqueous sodium chloride solution
  3. dry with materialDry the organic layer over Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate in vacuo
  6. customto obtain a residue
  7. customEvaporate the product
  8. additioncontaining fractions
  9. custompartition between dichloromethane and 1/1 brine/water
  10. dry with materialDry the organic layer over Na2SO4
  11. filtrationfilter
  12. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-e2dc7ef66552441988bd284e10b849d5
Source dataset
uspto-grants-2001_04
Patent number
US06211199B1

Linked notes

Loading…