Diisopropylethylamine → 1-(3,4,5-trimethoxybenzyl)-3-(3-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)propyl)-3-(4-fluorophenylmethyl)-2-oxopyrrolidine

HRID 323281Notes

Reaction equation

HRID 323281 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:29]=[C:30]([O:34][CH3:35])[C:31]=1[O:32][CH3:33])[CH2:6][N:7]1[CH2:11][CH2:10][C:9]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)([CH2:12][CH2:13][CH2:14]OS(C)(=O)=O)[C:8]1=[O:28].[CH2:36]([O:38][CH2:39][CH2:40][N:41]1[C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][C:44]=2[N:43]=[C:42]1[NH:50][CH:51]1[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]1)[CH3:37].C(N(CC)C(C)C)(C)C.CO.C(OCC)(=O)C>C(#N)C.C(OCC)(=O)C.ClCCl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:29]=[C:30]([O:34][CH3:35])[C:31]=1[O:32][CH3:33])[CH2:6][N:7]1[CH2:11][CH2:10][C:9]([CH2:12][CH2:13][CH2:14][N:54]2[CH2:53][CH2:52][CH:51]([NH:50][C:42]3[N:41]([CH2:40][CH2:39][O:38][CH2:36][CH3:37])[C:45]4[CH:46]=[CH:47][CH:48]=[CH:49][C:44]=4[N:43]=3)[CH2:56][CH2:55]2)([CH2:20][C:21]2[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=2)[C:8]1=[O:28]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 13808350(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)(piperidin-4-yl)amineHCID 184644831-(3,4,5-Trimethoxybenzyl)-3-(4-fluorophenylmethyl)-3-(3-methanesulfonyloxypropyl)-2-oxopyrrolidineHCID 21584119Ethylacetate methanol

Product 1

HCID 99181341-(3,4,5-trimethoxybenzyl)-3-(3-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)propyl)-3-(4-fluorophenylmethyl)-2-oxopyrrolidine

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Combine 1-(3,4,5-trimethoxybenzyl)-3-(4-fluorophenylmethyl)-3-(3-methanesulfonyloxypropyl)-2-oxopyrrolidine (0.43 g, 1.50 mmol), (1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)(piperidin-4-yl)amine (0.74 g, 1.46 mmol), and N,N-diisopropylethylamine (0.39 g, 3.0 mmol) in acetonitrile (10 mL). Heat to reflux. After 12 hours, dilute the reaction mixture with ethyl acetate and extract twice with water. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 10% methanol/ethyl acetate/2% triethylamine. Combine the product containing fractions and evaporate in vacuo to give a residue. Combine the residue and dichloromethane and extract with brine. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give the title compound.

Workup

  1. temperatureHeat to reflux
  2. extractionextract twice with water
  3. dry with materialDry the organic layer over Na2SO4
  4. filtrationfilter
  5. customevaporate in vacuo
  6. customto give a residue
  7. additioncontaining fractions
  8. customevaporate in vacuo
  9. customto give a residue
  10. extractionextract with brine
  11. dry with materialDry the organic layer over Na2SO4
  12. filtrationfilter
  13. customevaporate in vacuo

Sources & evidence

ORD record
ord-30ddb03907a843ec96a932df62f2b897
Source dataset
uspto-grants-2001_04
Patent number
US06211199B1

Reaction notes

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