N-Hydroxysuccinimide → HCID 21998976, compound

HRID 1976612Notes

Reaction equation

HRID 1976612 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][CH2:8][CH2:9][NH2:10])[CH:2]=1.[CH3:11][O:12][C:13]1[CH:14]=[C:15]([CH2:21][CH2:22][CH2:23][C:24](O)=O)[CH:16]=[CH:17][C:18]=1[O:19][CH3:20].ON1C(=O)CCC1=O.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl.O1CCCC1.CO>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][CH2:8][CH2:9][NH:10][CH2:24][CH2:23][CH2:22][CH2:21][C:15]2[CH:16]=[CH:17][C:18]([O:19][CH3:20])=[C:13]([O:12][CH3:11])[CH:14]=2)[CH:2]=1

Participants

8

Reactant 4

HCID 80170N-HydroxysuccinimideHCID 3236754-(3,4-Dimethoxyphenyl)butanoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 135575233-(Pyridin-3-yl)propan-1-amine

Product 1

HCID 21998976HCID 21998976, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A stirred solution of 3-(3-pyridyl)propylamine (517.8 mg, 1.679 mmoles), 4-(3,4-dimethoxyphenyl)butanoic acid (376.5 mg, 1 equiv.) and N-hydroxysuccinimide (193.2 mg, 1.1 equiv.) in methylene chloride (15 mL) at 0° C. was treated with EDC hydrochloride (353.1 mg, 1.1 equiv.). The mixture was allowed to warm to room temperature after 10 minutes. Stirring was continued for 16 hours and then the solvent was removed under reduced pressure. The residue was partitioned between ethyl acetate and water. The aqueous phase was re-extracted with ethyl acetate. The combined organic phases were washed with water and brine, dried over sodium sulfate and evaporated to give a colorless oil. This crude amide was dissolved in dry tetrahydrofuran (5 mL) under argon. The solution was cooled to 0° C. and then treated with 1 M borane-tetrahydrofuran complex (7.0 mL, 4 equiv.). The mixture was heated at reflux for 16 hours and then cooled to room temperature. Dry methanol (10 mL) was added carefully to the stirred mixture to avoid foaming. The resulting solution was evaporated under reduced pressure and the residue dissolved in dry methanol (20 mL). The mixture was heated at reflux for 4 hours and then evaporated. The crude amine was carried on without purification.

Workup

  1. customthe solvent was removed under reduced pressure
  2. customThe residue was partitioned between ethyl acetate and water
  3. extractionThe aqueous phase was re-extracted with ethyl acetate
  4. washThe combined organic phases were washed with water and brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customto give a colorless oil
  8. temperatureThe solution was cooled to 0° C.
  9. additiontreated with 1 M borane-tetrahydrofuran complex (7.0 mL, 4 equiv.)
  10. temperatureThe mixture was heated
  11. temperatureat reflux for 16 hours
  12. temperaturecooled to room temperature
  13. customThe resulting solution was evaporated under reduced pressure
  14. dissolutionthe residue dissolved in dry methanol (20 mL)
  15. temperatureThe mixture was heated
  16. temperatureat reflux for 4 hours
  17. customevaporated
  18. customThe crude amine was carried on without purification

Sources & evidence

ORD record
ord-16a365ce7f2a4838a8ab96279f037709
Source dataset
uspto-grants-2001_05
Patent number
US06228872B1

Reaction notes

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