Sodium Bicarbonate → (1-{2-[1-Benzoyl-3-(3,4-dimethoxy-phenyl)-pyrrolidin-3-yl]-ethyl}-piperidin-4-yl)-[1-(4-fluoro-benzyl)-1H-benzoimidazol-2-yl]-methanone

HRID 2269838Notes

Reaction equation

HRID 2269838 reaction equation
[C:1]([N:9]1[CH2:13][CH2:12][C:11]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[CH:21]=2)([CH2:14][CH2:15]S(C)(=O)=O)[CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:30][C:31]1[CH:54]=[CH:53][C:34]([CH2:35][N:36]2[C:40]3[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=3[N:38]=[C:37]2[C:45]([CH:47]2[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]2)=[O:46])=[CH:33][CH:32]=1.C(=O)(O)[O-].[Na+].C(OCC)(=O)C.CO>O1CCCC1.O.ClCCl>[C:1]([N:9]1[CH2:13][CH2:12][C:11]([CH2:14][CH2:15][N:50]2[CH2:51][CH2:52][CH:47]([C:45]([C:37]3[N:36]([CH2:35][C:34]4[CH:33]=[CH:32][C:31]([F:30])=[CH:54][CH:53]=4)[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:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[CH:21]=2)[CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 155428834-(1-(4-fluorobenzyl)-1H-benzimidazole-2-carbonyl)piperidineHCID 155428841-Benzoyl-3-(3,4-dimethoxy-phenyl)-3-(2-methanesulfonyl-ethyl)-pyrrolidineHCID 21584119Ethylacetate methanol

Product 1

HCID 10190056(1-{2-[1-Benzoyl-3-(3,4-dimethoxy-phenyl)-pyrrolidin-3-yl]-ethyl}-piperidin-4-yl)-[1-(4-fluoro-benzyl)-1H-benzoimidazol-2-yl]-methanone

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21881883Oxolane--water (1/1)Solvent

Procedure

Combine 1-benzoyl-3-(3,4-dimethoxy-phenyl)-3-(2-methanesulfonyl-ethyl)-pyrrolidine (0.54 g, 1.3 mmol) and 4-[1-(4-fluoro-benzyl)-1 H-benzoimidazole-2-carbonyl]-piperidine (0.46 g, 1.4 mmol), and sodium bicarbonate (0.2 g, 2.5 mmol) in tetrahydrofuran/water (15/4) (30 mL). Heat to reflux. After 48 hours, cool to ambient temperature. After 72 hours, evaporate in vacuo to obtain a residue. Partition the residue between dichloromethane/chloroform and 5% sodium bicarbonate 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 a solid. Combine the solid 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 82° C. to give the title compound: Rf=0.28 (silica gel, 5/1 ethyl acetate/methanol); mp; 88-90° C. Elemental Analysis calculated for C41H43FN4O4: C 72.20; H 6.47; N 8.21; Found: C 71.96; H 6.38; N 8.17.

Workup

  1. temperatureHeat to reflux
  2. waitAfter 72 hours
  3. customevaporate in vacuo
  4. customto obtain a residue
  5. customPartition the residue between dichloromethane/chloroform and 5% sodium bicarbonate solution
  6. dry with materialDry the organic layer over Na2SO4
  7. filtrationfilter
  8. concentrationconcentrate in vacuo
  9. customto obtain a residue
  10. extractionextract with 5% sodium bicarbonate solution
  11. dry with materialDry the organic layer over Na2SO4
  12. filtrationfilter
  13. concentrationconcentrate in vacuo
  14. customto obtain a residue
  15. customDry the residue in vacuo at 82° C.

Sources & evidence

ORD record
ord-61f477c809f144bda7c57dccd8586558
Source dataset
uspto-grants-2001_12
Patent number
US06329392B1

Reaction notes

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