1,1'-Carbonyldiimidazole → HCID 19883426, compound

HRID 846608Notes

Reaction equation

HRID 846608 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]([OH:12])=[O:11])=[CH:2]1.[CH3:13][N:14](C)C=O.[O:18]1[CH2:22][CH2:21][CH2:20][CH2:19]1.[C:23](N1C=CN=C1)([N:25]1[CH:29]=[CH:28]N=C1)=O.[C:35]([OH:42])(=[O:41])/[CH:36]=[CH:37]/[C:38]([OH:40])=[O:39]>CO>[OH2:11].[C:35]([OH:42])(=[O:41])/[CH:36]=[CH:37]/[C:38]([OH:40])=[O:39].[OH:18][C:22]1([CH2:13][NH:14][C:10]([C:3]2[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[NH:1][CH:2]=2)=[O:12])[CH:21]2[CH2:28][CH2:29][N:25]([CH2:19][CH2:20]2)[CH2:23]1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 69867Indole-3-Carboxylic AcidHCID 444972Fumaric AcidHCID 21974620tetrahydrofuran N,N-dimethylformamide

Product 1

HCID 19883426HCID 19883426, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A suspension of indole-3-carboxylic acid (1.94 g, 0.012 mole) in anhydrous 2:1 dimethylformamide/tetrahydrofuran (15 ml) under nitrogen was treated with 1,1'-carbonyldiimidazole (2.27 g, 0.014 mole), stirred for two hours, and degassed over 15 minutes with a stream of nitrogen. A solution containing 3-aminomethyl-1-azabicyclo[2.2.2]octan-3-ol in tetrahydrofuran (10 ml) was added and the mixture stirred for 18 hours at 25° C. and for four hours at 50° C., then concentrated in vacuo. The residue was partitioned between saturated sodium carbonate (75 ml) and toluene (150 ml) containing some 2-propanol, and the organic layer was separated. The aqueous solution was extracted with toluene (75 ml) containing some 2-propanol, and the combined organic solution was dried (sodium sulfate), and concentrated in vacuo. The gummy residue was washed with water, redissolved in toluene containing some 2-propanol, dried (sodium sulfate), concentrated in vacuo, and taken up in methanol (20 ml). A warm solution of fumaric acid (2.0 g, 0.0172 mole) in methanol (30 ml) was added, and after 15 minutes the solution was concentrated in vacuo to a gummy oil. This was triturated successively from ether, acetonitrile, and ethyl acetate to afford (after drying) 3.36 g (52%) of the title compound as a colorless solid.

Workup

  1. customdegassed over 15 minutes with a stream of nitrogen
  2. additionA solution containing 3-aminomethyl-1-azabicyclo[2.2.2]octan-3-ol in tetrahydrofuran (10 ml)
  3. additionwas added
  4. stirringthe mixture stirred for 18 hours at 25° C. and for four hours at 50° C.
  5. concentrationconcentrated in vacuo
  6. customThe residue was partitioned between saturated sodium carbonate (75 ml) and toluene (150 ml)
  7. additioncontaining some 2-propanol
  8. customthe organic layer was separated
  9. extractionThe aqueous solution was extracted with toluene (75 ml)
  10. additioncontaining some 2-propanol
  11. dry with materialthe combined organic solution was dried (sodium sulfate)
  12. concentrationconcentrated in vacuo
  13. washThe gummy residue was washed with water
  14. dissolutionredissolved in toluene containing some 2-propanol
  15. dry with materialdried (sodium sulfate)
  16. concentrationconcentrated in vacuo
  17. concentrationafter 15 minutes the solution was concentrated in vacuo to a gummy oil
  18. customThis was triturated successively from ether, acetonitrile, and ethyl acetate
  19. customto afford
  20. dry with material(after drying) 3.36 g (52%) of the title compound as a colorless solid

Sources & evidence

ORD record
ord-5de72bc47e54417b811013b27294266d
Source dataset
uspto-grants-1992_08
Patent number
US05137895

Reaction notes

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