Diisopropylethylamine → 1-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1-(4-fluorobenzyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-(3,4-dichlorophenyl)pyrrolidine

HRID 323201

Reaction equation

HRID 323201 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:28]=[C:29]([O:33][CH3:34])[C:30]=1[O:31][CH3:32])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)([CH2:13][CH2:14]OS(C)(=O)=O)[CH2:9]1)=[O:7].[F:35][C:36]1[CH:58]=[CH:57][C:39]([CH2:40][N:41]2[C:45]3[CH:46]=[CH:47][CH:48]=[CH:49][C:44]=3[N:43]=[C:42]2[NH:50][CH:51]2[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]2)=[CH:38][CH:37]=1.C(N(CC)C(C)C)(C)C.CO.C(OCC)(=O)C>C(#N)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:28]=[C:29]([O:33][CH3:34])[C:30]=1[O:31][CH3:32])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:13][CH2:14][N:54]2[CH2:55][CH2:56][CH:51]([NH:50][C:42]3[N:41]([CH2:40][C:39]4[CH:57]=[CH:58][C:36]([F:35])=[CH:37][CH:38]=4)[C:45]4[CH:46]=[CH:47][CH:48]=[CH:49][C:44]=4[N:43]=3)[CH2:52][CH2:53]2)([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)[CH2:9]1)=[O:7]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 123618TecastemizoleHCID 158408993-(3,4-Dichlorophenyl)-1-(3,4,5-trimethoxybenzoyl)-3-pyrrolidineethanol methansulfonateHCID 21584119Ethylacetate methanol2×

Product 1

HCID 98754181-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1-(4-fluorobenzyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-(3,4-dichlorophenyl)pyrrolidine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Combine 1-(3,4,5-trimethoxybenzoyl)-3-(3,4-dichlorophenyl)-3-(2-methanesulfonyloxyethyl)pyrrolidine (0.52 g, 0.98 mmol) and (1-(4-fluorobenzyl)-1H-benzimidazol-2-yl)(piperidin-4-yl)amine (0.49 g, 1.5 mmol), and N,N-diisopropylethylamine (0.4 mL, 2.3 mmol) in acetonitrile (12 mL). Heat to reflux. After 18 hours, cool and partition the reaction mixture between ethyl acetate and water. Separate the layers and extract the organic layer with water, saturated aqueous sodium bicarbonate, and brine. 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 5% methanol/ethyl acetate and then 50% methanol/ethyl acetate to give a residue. Partition the residue between chloroform and brine. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to give the title compound: Rf=0.39 (silica gel, 30% methanol/ethyl acetate).

Workup

  1. temperatureHeat to reflux
  2. temperaturecool
  3. custompartition the reaction mixture between ethyl acetate and water
  4. customSeparate the layers
  5. extractionextract the organic layer with water, saturated aqueous sodium bicarbonate, and brine
  6. dry with materialDry the organic layer over Na2SO4
  7. filtrationfilter
  8. concentrationconcentrate in vacuo
  9. customto obtain a residue
  10. customPartition the residue between chloroform and brine
  11. dry with materialDry the organic layer over Na2SO4
  12. filtrationfilter
  13. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-bff7e6b31cb440a2b262322bb11d46ca
Source dataset
uspto-grants-2001_04
Patent number
US06211199B1

Linked notes

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