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

HRID 323190Notes

Reaction equation

HRID 323190 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:30]=[C:31]([O:35][CH3:36])[C:32]=1[O:33][CH3:34])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[CH:21]=2)([CH2:13][CH2:14]OS(C)(=O)=O)[CH2:9]1)=[O:7].[CH2:37]([O:39][CH2:40][CH2:41][N:42]1[C:46]2[CH:47]=[CH:48][CH:49]=[CH:50][C:45]=2[N:44]=[C:43]1[NH:51][CH:52]1[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]1)[CH3:38].C(N(CC)C(C)C)(C)C.C(OCC)(=O)C.CO>C(#N)C.ClCCl>[CH3:36][O:35][C:31]1[CH:30]=[C:5]([CH:4]=[C:3]([O:2][CH3:1])[C:32]=1[O:33][CH3:34])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:13][CH2:14][N:55]2[CH2:54][CH2:53][CH:52]([NH:51][C:43]3[N:42]([CH2:41][CH2:40][O:39][CH2:37][CH3:38])[C:46]4[CH:47]=[CH:48][CH:49]=[CH:50][C:45]=4[N:44]=3)[CH2:57][CH2:56]2)([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[CH:21]=2)[CH2:9]1)=[O:7]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 13808350(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)(piperidin-4-yl)amineHCID 184646141-(3,4,5-Trimethoxybenzoyl)-3-(3,4-dimethoxyphenyl)-3-(2-methanesulfonyloxyethyl)pyrrolidineHCID 21584119Ethylacetate methanol

Product 1

HCID 98965901-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-(3,4-dimethoxyphenyl)pyrrolidine

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

Combine 1-(3,4,5-trimethoxybenzoyl)-3-(3,4-dimethoxyphenyl)-3-(2-methanesulfonyloxyethyl)pyrrolidine (0.51 g, 0.97 mmol) and (1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)(piperidin-4-yl)amine (0.34 g, 1.2 mmol), and N,N-diisopropylethylamine (0.25 g, 1.9 mmol) in acetonitrile (5 mL). Heat to reflux. After 54 hours, partition the residue between ethyl acetate and 5% sodium bicarbonate solution. Separate the layers and extract the organic layer with 5% sodium bicarbonate and then water. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Chromatograph the residue on silica gel eluting with 1/1 ethyl acetate/methanol to give a residue. Combine the residue with dichloromethane and extract with water. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Dry the residue in vacuo at 60° C. to give the title compound: Rf=0.37 (silica gel, 1/1 ethyl acetate/methanol).

Workup

  1. temperatureHeat to reflux
  2. custompartition the residue between ethyl acetate and 5% sodium bicarbonate solution
  3. customSeparate the layers
  4. extractionextract the organic layer with 5% sodium bicarbonate
  5. dry with materialDry the organic layer over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. customto obtain a residue
  9. extractionextract with water
  10. dry with materialDry the organic layer over Na2SO4
  11. filtrationfilter
  12. concentrationconcentrate in vacuo
  13. customto obtain a residue
  14. customDry the residue in vacuo at 60° C.

Sources & evidence

ORD record
ord-7821d83417814506a5250512fdb0d3b8
Source dataset
uspto-grants-2001_04
Patent number
US06211199B1

Reaction notes

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