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

HRID 2269904Notes

Reaction equation

HRID 2269904 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].[NH:36]1[C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=2[N:38]=[C:37]1[C:45]([CH:47]1[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]1)=[O:46].C(N(C(C)C)CC)(C)C.C(#N)C>C(OCC)(=O)C>[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:50]2[CH2:51][CH2:52][CH:47]([C:45]([C:37]3[NH:36][C:40]4[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=4[N:38]=3)=[O:46])[CH2:48][CH2:49]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

6

Reactant 4

HCID 6342AcetonitrileHCID 81531DiisopropylethylamineHCID 155428821-(3,4,5-Trimethoxy-benzoyl)-3-(3,4-dimethoxy-phenyl)-3-(2-methanesulfonyl-ethyl)-pyrrolidineHCID 183332774-[1H-benzoimidazole-2-carbonyl]-piperidine

Product 1

HCID 103050691-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1H-benzoimidazole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(3,4-dimethoxy-phenyl)-pyrrolidine

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Combine 1-(3,4,5-trimethoxy-benzoyl)-3-(3,4-dimethoxy-phenyl)-3-(2-methanesulfonyl-ethyl)-pyrrolidine (1.19 g, 2.27 mmol), 4-[1H-benzoimidazole-2-carbonyl]-piperidine (1.65 g, 3.41 mmol) and diisopropylethylamine (1.47 g, 11.35 mmol) and acetonitrile (11 mL). Reflux the reaction mixture overnight, dilute with ethyl acetate and extract successively with a saturated aqueous NH4Cl solution, 5% aqueous NaHCO3 solution, water and saturated aqueous NaCl solution. Separate the organic layer, dry over anhydrous Na2So4, filter and remove the solvent in vacuo. Chromatograph the residue on silica gel eluting with ethyl acetate/methanol (5/1), evaporate the solvent and dry overnight at 82° C. at 0.20 torr to yield title compound: mp; 113.0-116.0° .C, Rf=0.23 (silica gel, 5/1 ethyl acetate/methanol). Elemental Analysis calculated for C37H44N4O7: C 67.66; H 6.75; N 8.53; Found: C 67.00; H 6.77; N 8.39.

Workup

  1. temperatureReflux the reaction mixture overnight
  2. extractionextract successively with a saturated aqueous NH4Cl solution, 5% aqueous NaHCO3 solution, water and saturated aqueous NaCl solution
  3. customSeparate the organic layer
  4. customdry over anhydrous Na2So4
  5. filtrationfilter
  6. customremove the solvent in vacuo
  7. customChromatograph the residue on silica gel eluting with ethyl acetate/methanol (5/1), evaporate the solvent
  8. customdry overnight at 82° C. at 0.20 torr

Sources & evidence

ORD record
ord-614d568134544777a1b1b9835585e770
Source dataset
uspto-grants-2001_12
Patent number
US06329392B1

Reaction notes

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