1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-[(R)-1-{3-(1-tert-butoxycarbonyl-4-piperidyl)propionyl}-3-piperidylcarbonyl]-3-ethynyl-beta-alanine ethyl ester

HRID 843733Notes

Reaction equation

HRID 843733 reaction equation
Cl.NC[CH:4](C#C)[C:5]([O:7][CH2:8][CH3:9])=[O:6].[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([CH2:25][CH2:26][C:27]([N:29]2[CH2:34][CH2:33][CH2:32][C@@H:31](C(O)=O)[CH2:30]2)=[O:28])[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].[OH:38]N1C2C=CC=CC=2N=N1.C(N=C=N[CH2:53][CH2:54][CH2:55][N:56]([CH3:58])C)C>CN(C)C=O.O>[CH2:8]([O:7][C:5](=[O:6])[CH2:4][CH:55]([C:54]#[CH:53])[NH:56][C:58]([C@@H:31]1[CH2:32][CH2:33][CH2:34][N:29]([C:27](=[O:28])[CH2:26][CH2:25][CH:22]2[CH2:21][CH2:20][N:19]([C:17]([O:16][C:12]([CH3:13])([CH3:14])[CH3:15])=[O:18])[CH2:24][CH2:23]2)[CH2:30]1)=[O:38])[CH3:9]

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 22611856Ethyl 3-amino-2-ethynylpropionate hydrochlorideHCID 54408184(R)-1-(3-(1-tert-butoxycarbonyl-4-piperidyl)propionyl]-3-piperidinecarboxylic acid

Product 1

HCID 86584068N-[(R)-1-{3-(1-tert-butoxycarbonyl-4-piperidyl)propionyl}-3-piperidylcarbonyl]-3-ethynyl-beta-alanine ethyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of ethyl 3-amino-2-ethynylpropionate hydrochloride (0.5 g), (R)-1-[3-(1-tert-butoxycarbonyl-4-piperidyl)propionyl]-3-piperidinecarboxylic acid (1.04 g) and 1-hydroxybenztriazole (0.38 g) in N,N-dimethylformamide (5 ml) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (0.51 ml) under stirring at 0° C. After stirring at ambient temperature overnight, the mixture was poured into water and extracted with ethyl acetate. The extract was washed with water, brine and dried over MgSO4, and evaporated in vacuo. The residue was purified by chromatography on silica gel eluting with CHCl3:MeOH=(100:1) to give N-[(R)-1-{3-(1-tert-butoxycarbonyl-4-piperidyl)propionyl}-3-piperidylcarbonyl]-3-ethynyl-β-alanine ethyl ester as an oil (1.38 g).

Workup

  1. stirringAfter stirring at ambient temperature overnight
  2. extractionextracted with ethyl acetate
  3. washThe extract was washed with water, brine
  4. dry with materialdried over MgSO4
  5. customevaporated in vacuo
  6. customThe residue was purified by chromatography on silica gel eluting with CHCl3

Sources & evidence

ORD record
ord-d7c9d268afa44dc3a8129143b0ad6cff
Source dataset
uspto-grants-2002_04
Patent number
US06380215B1

Reaction notes

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