Acetonitrile → 5-[2-(2-acetylamino-ethylcarbamoyl)-ethyl]-3-methyl-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester

HRID 2191502Notes

Reaction equation

HRID 2191502 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7]([CH3:23])=[C:8]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[NH:9][C:10]=1[CH2:11][CH2:12][C:13]([OH:15])=O)=[O:5])[CH3:2].[OH:24]N1C2C=CC=CC=2N=N1.C(N=C=NC[CH2:40][CH2:41][N:42]([CH3:44])C)C.[C:45](#[N:47])C>>[CH2:1]([O:3][C:4]([C:6]1[C:7]([CH3:23])=[C:8]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[NH:9][C:10]=1[CH2:11][CH2:12][C:13](=[O:15])[NH:47][CH2:45][CH2:44][NH:42][C:41](=[O:24])[CH3:40])=[O:5])[CH3:2]

Participants

5

Reactant 4

HCID 6342AcetonitrileHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 592501015-(2-carboxy-ethyl)-3-methyl-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester

Product 1

HCID 592500615-[2-(2-acetylamino-ethylcarbamoyl)-ethyl]-3-methyl-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl esterYield 65%

Procedure

5-(2-Carboxy-ethyl)-3-methyl-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester 1e (9.85 g, 30.3 mmol) obtained from step 4 of Example 1 was dissolved in acetonitrile (50 ml) under stirring, and added with 1-hydroxy-1H-benzotriazole (8.2 g, 60.6 mmol) and N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide (11.6 g, 60.6 mmol) to the solution at room temperature. Upon completion of the addition, the reaction mixture was stirred at room temperature overnight. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was concentrated under reduced pressure, added with water (200 ml), and exacted with ethyl acetate (200 ml×4). The combined organic extracts were washed with saturated brine (100 ml), dried over anhydrous magnesium sulfate, filtered to remove the drying agent and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound 5-[2-(2-acetylamino-ethylcarbamoyl)-ethyl]-3-methyl-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester 62a (8 g, yield 65%) as a white solid.

Workup

  1. additionUpon completion of the addition
  2. stirringthe reaction mixture was stirred at room temperature overnight
  3. concentrationthe reaction mixture was concentrated under reduced pressure
  4. additionadded with water (200 ml)
  5. washThe combined organic extracts were washed with saturated brine (100 ml)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customto remove the drying agent
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-7901a6faa97d4a79bcaebd3206f479c3
Source dataset
uspto-grants-2012_12
Patent number
US08329682B2

Reaction notes

Loading…