N-(2-Aminoethyl)piperidine → 4-methyl-2-[(2-piperidin-1-yl-ethyl carbamoyl)-methyl]-1H-pyrrole-3-carboxylic acid ethyl ester

HRID 905746

Reaction equation

HRID 905746 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:10]([CH3:11])=[CH:9][NH:8][C:7]=1[CH2:12][C:13]([OH:15])=O)=[O:5])[CH3:2].[N:16]1([CH2:22][CH2:23][NH2:24])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1>CN(C)C=O.ClCCl.O>[CH2:1]([O:3][C:4]([C:6]1[C:10]([CH3:11])=[CH:9][NH:8][C:7]=1[CH2:12][C:13](=[O:15])[NH:24][CH2:23][CH2:22][N:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 33944N-(2-Aminoethyl)piperidineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 498403282-carboxymethyl-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester

Product 1

HCID 666145154-methyl-2-[(2-piperidin-1-yl-ethyl carbamoyl)-methyl]-1H-pyrrole-3-carboxylic acid ethyl esterYield 85%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A stirred solution of 2-carboxymethyl-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester (2.67 g, 12.67 mmol) in N,N-dimethylformamide (6.5 ml) and dichloromethane (65 ml) was added with 2-piperidin-1-yl-ethylamine (1.78 g, 13.9 mmol), N-ethyl-N′-(dimethylaminopropyl)-carbodiimide hydrochloride (4.84 g, 25.34 mmol) and 1-hydroxybenzotriazol (1.71 g, 12.67 mmol) in an ice/water-bath. Upon completion of the addition, the reaction mixture was stirred at room temperature overnight, then added with cold water (50 ml), and extracted with dichloromethane (50 ml×3). The combined organic extracts were washed with saturated sodium bicarbonate (50 ml), water (50 ml), brine (50 ml), dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 4-methyl-2-[(2-piperidin-1-yl-ethyl carbamoyl)-methyl]-1H-pyrrole-3-carboxylic acid ethyl ester (3.46 g, 85%) as a brown oil which was used as such.

Workup

  1. additionUpon completion of the addition
  2. extractionextracted with dichloromethane (50 ml×3)
  3. washThe combined organic extracts were washed with saturated sodium bicarbonate (50 ml), water (50 ml), brine (50 ml)
  4. dry with materialdried with anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-7a886fb7eeda4224b377e749aead6f7f
Source dataset
uspto-grants-2011_09
Patent number
US08012966B2

Linked notes

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