1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 73991054, compound

HRID 2414687Notes

Reaction equation

HRID 2414687 reaction equation
[NH:1]1[CH2:8][CH:7]([C:9]([O:11]CC)=O)[CH2:6][CH:5]=[CH:4][CH2:3][CH2:2]1.[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][CH:24]([C:27](O)=O)[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].[OH:30]N1C2C=CC=CC=2N=N1.Cl.[CH3:41][O:42][C:43](=[O:47])[CH2:44][CH2:45][NH2:46].CCN=C=NC[CH2:54][CH2:55]N(C)C>CN(C=O)C>[CH3:41][O:42][C:43](=[O:47])[CH2:44][CH2:45][NH:46][C:9]([CH:7]1[CH2:8][N:1]([C:54](=[O:30])[CH2:55][CH2:27][CH:24]2[CH2:23][CH2:22][N:21]([C:19]([O:18][C:14]([CH3:15])([CH3:16])[CH3:17])=[O:20])[CH2:26][CH2:25]2)[CH2:2][CH2:3][CH:4]=[CH:5][CH2:6]1)=[O:11]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-Hydroxybenzotriazole2×HCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 2734767Methyl 3-aminopropanoate hydrochlorideHCID 69818122HCID 69818122, compound

Product 1

HCID 73991054HCID 73991054, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of ethyl 1,2,3,6,7,8-hexahydroazocine-7-carboxylate (65 mg, 0.35 mmol), 1-(tert-butoxycarbonyl)-piperidine-4-carboxylic acid (91 mg, 0.35 mmol), 1-hydroxybenztriazole (HOBT) (48 mg, 0.35 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodimde hydrochloride (WSC.HCl) (68 mg, 0.35 mmol) in DMF was stirred overnight at room temperature. The mixture was quenched by a saturated aqueous NaHCO3 solution, then extracted with ethyl acetate. The extract was washed with water and brine, dried over Na2SO4, and evaporated in vacuo. The residue was dissolved in THF (3 mL), and 1N aqueous LiOH (0.9 mL) was added thereto. After stiring for an hour, the mixture was acidified to pH 2.5 with 20% aqueous KHSO4 solution, and extracted with ethyl acetate. The extract was dried over Na2SO4, and evaporated in vacuo. The residue was dissolved in DMF (5 mL). To the solution was added β-alanine methyl ester hydrochloride (42 mg, 0.30 mmol), HOBT (41 mg, 0.30 mmol) and WSC (55 mL, 0.30 mmol). After stirring for 2 hours, the mixture was quenched by a saturated aqueous NaHCO3 solution, then extracted with ethyl acetate. The extract was washed with water and brine, dried over Na2SO4, and evaporated in vacuo. The residue was purified by a silica gel column chromatography eluting with a mixture of ethyl acetate and n-hexane (1:10) to give N-{1-[3-[1-(tert-butoxycarbonyl)4-piperidinyl)propionyl]-1,2,3,6,7,8-hexahydroazocine-7-carbonyl}-β-alanine methyl ester (127 mg, 0.27 mmol, 68.3%) as a colourless oil.

Workup

  1. customThe mixture was quenched by a saturated aqueous NaHCO3 solution
  2. extractionextracted with ethyl acetate
  3. washThe extract was washed with water and brine
  4. dry with materialdried over Na2SO4
  5. customevaporated in vacuo
  6. dissolutionThe residue was dissolved in THF (3 mL)
  7. addition1N aqueous LiOH (0.9 mL) was added
  8. waitAfter stiring for an hour
  9. extractionextracted with ethyl acetate
  10. dry with materialThe extract was dried over Na2SO4
  11. customevaporated in vacuo
  12. dissolutionThe residue was dissolved in DMF (5 mL)
  13. stirringAfter stirring for 2 hours
  14. customthe mixture was quenched by a saturated aqueous NaHCO3 solution
  15. extractionextracted with ethyl acetate
  16. washThe extract was washed with water and brine
  17. dry with materialdried over Na2SO4
  18. customevaporated in vacuo
  19. customThe residue was purified by a silica gel column chromatography
  20. washeluting with a mixture of ethyl acetate and n-hexane (1:10)

Sources & evidence

ORD record
ord-a933fff189dc416a9d1fd487bfc777dd
Source dataset
uspto-grants-2004_11
Patent number
US06812235B2

Reaction notes

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