1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-[(R)-1-[3-(1-tert-butoxycarbonyl-4-piperidyl)-(E)-acryloyl]-3-piperidylcarbonyl]-3(R)-(3,4-dimethoxyphenethyl)-beta-alanine methyl ester

HRID 1934393Notes

Reaction equation

HRID 1934393 reaction equation
[CH3:1][O:2][C:3](=[O:19])[CH2:4][C@@H:5]([CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[C:11]([O:17][CH3:18])[CH:10]=1)[NH2:6].[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][CH:30](/[CH:33]=[CH:34]/[C:35]([N:37]2[CH2:42][CH2:41][CH2:40][C@@H:39]([C:43](O)=[O:44])[CH2:38]2)=[O:36])[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21].ON1C2C=CC=CC=2N=N1.C(N=C=NCCCN(C)C)C>CN(C)C=O.O>[CH3:1][O:2][C:3](=[O:19])[CH2:4][C@@H:5]([CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[C:11]([O:17][CH3:18])[CH:10]=1)[NH:6][C:43]([C@@H:39]1[CH2:40][CH2:41][CH2:42][N:37]([C:35](=[O:36])/[CH:34]=[CH:33]/[CH:30]2[CH2:31][CH2:32][N:27]([C:25]([O:24][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:26])[CH2:28][CH2:29]2)[CH2:38]1)=[O:44]

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 69817990(R)-1-[3-(1-tert-butoxycarbonyl-4-piperidyl)-(E)-acryloyl]-3-piperidinecarboxylic acidHCID 867580313(R)-(3,4-dimethoxyphenethyl)-beta-alanine methyl ester

Product 1

HCID 86758030N-[(R)-1-[3-(1-tert-butoxycarbonyl-4-piperidyl)-(E)-acryloyl]-3-piperidylcarbonyl]-3(R)-(3,4-dimethoxyphenethyl)-beta-alanine methyl esterYield 91.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 3(R)-(3,4-dimethoxyphenethyl)-β-alanine methyl ester (0.87 g), (R)-1-[3-(1-tert-butoxycarbonyl-4-piperidyl)-(E)-acryloyl]-3-piperidinecarboxylic acid (1.19 g) and 1-hydroxybenztriazole (0.44 g) in dimethylformamide (9 ml) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (0.59 ml) at 0° C. The reaction mixture was stirred overnight at room temperature, and then poured into water. The whole was extracted with ethyl acetate, washed with aqueous saturated NaHCO3, water, and brine, dried over MgSO4, and evaporated in vacuo, subsequently. The residue was purified by column chromatography on silica gel eluting with ethyl acetate: n-hexane=(5:1) to give N-[(R)-1-[3-(1-tert-butoxycarbonyl-4-piperidyl)-(E)-acryloyl]-3-piperidylcarbonyl]-3(R)-(3,4-dimethoxyphenethyl)-β-alanine methyl ester as a colorless oil (1.83 g).

Workup

  1. extractionThe whole was extracted with ethyl acetate
  2. washwashed with aqueous saturated NaHCO3, water, and brine
  3. dry with materialdried over MgSO4
  4. customevaporated in vacuo
  5. customThe residue was purified by column chromatography on silica gel eluting with ethyl acetate

Sources & evidence

ORD record
ord-60d4fa9d85a64369a5c1d2c922d42e41
Source dataset
uspto-grants-2002_05
Patent number
US06384028B1

Reaction notes

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