Diisopropylethylamine → 1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(4-fluoro-benzyl)-1H-benzoimidazole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(3,4-dimethoxy-phenyl)-pyrrolidine

HRID 2269837Notes

Reaction equation

HRID 2269837 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])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH3:28])[CH:20]=2)([CH2:13][CH2:14]S(C)(=O)=O)[CH2:9]1)=[O:7].[F:36][C:37]1[CH:60]=[CH:59][C:40]([CH2:41][N:42]2[C:46]3[CH:47]=[CH:48][CH:49]=[CH:50][C:45]=3[N:44]=[C:43]2[C:51]([CH:53]2[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]2)=[O:52])=[CH:39][CH:38]=1.C(N(C(C)C)CC)(C)C.C(OCC)(=O)C.CO>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])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:13][CH2:14][N:56]2[CH2:57][CH2:58][CH:53]([C:51]([C:43]3[N:42]([CH2:41][C:40]4[CH:39]=[CH:38][C:37]([F:36])=[CH:60][CH:59]=4)[C:46]4[CH:47]=[CH:48][CH:49]=[CH:50][C:45]=4[N:44]=3)=[O:52])[CH2:54][CH2:55]2)([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH3:28])[CH:20]=2)[CH2:9]1)=[O:7]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 155428821-(3,4,5-Trimethoxy-benzoyl)-3-(3,4-dimethoxy-phenyl)-3-(2-methanesulfonyl-ethyl)-pyrrolidineHCID 155428834-(1-(4-fluorobenzyl)-1H-benzimidazole-2-carbonyl)piperidineHCID 21584119Ethylacetate methanol

Product 1

HCID 99185761-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(4-fluoro-benzyl)-1H-benzoimidazole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(3,4-dimethoxy-phenyl)-pyrrolidine

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Combine 1-(3,4,5-trimethoxy-benzoyl)-3-(3,4-dimethoxy-phenyl)-3-(2-methanesulfonyl-ethyl)-pyrrolidine (0.5 g, 0.96 mmol) and 4-[1-(4-fluoro-benzyl)-1 H-benzoimidazole-2-carbonyl]-piperidine (0.49 g, 1.44 mmol), and diisopropylethylamine (0.33 mL, 1.92 mmol) in acetonitrile (5 mL). Heat to reflux. After 18 hours, cool and dilute with ethyl acetate. Extract twice with 5% sodium bicarbonate solution, twice with water, and with saturated sodium chloride solution. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Chromatograph the residue on silica gel eluting with 5/1 ethyl acetate/methanol to give an oil. Combine the oil with dichloromethane and extract with 5% sodium bicarbonate solution. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Dry the residue in vacuo at 65° C. to give the title compound: Rf=0.27 (silica gel, 5/1 ethyl acetate/methanol).

Workup

  1. temperatureHeat to reflux
  2. temperaturecool
  3. extractionExtract twice with 5% sodium bicarbonate solution, twice with water
  4. dry with materialDry the organic layer over Na2SO4
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customto obtain a residue
  8. extractionextract with 5% sodium bicarbonate solution
  9. dry with materialDry the organic layer over Na2SO4
  10. filtrationfilter
  11. concentrationconcentrate in vacuo
  12. customto obtain a residue
  13. customDry the residue in vacuo at 65° C.

Sources & evidence

ORD record
ord-dd5b053f55294c3cb86d7ee9bb95e623
Source dataset
uspto-grants-2001_12
Patent number
US06329392B1

Reaction notes

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