1-Hydroxybenzotriazole → 2-{[(4-hydroxy-1-methyl-piperidin-4-ylmethyl)-carbamoyl]-methyl}-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester

HRID 1811314Notes

Reaction equation

HRID 1811314 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].[NH2:16][CH2:17][C:18]1([OH:25])[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1>ClCCl.CN(C=O)C>[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:16][CH2:17][C:18]1([OH:25])[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 64842624-(Aminomethyl)-1-methylpiperidin-4-olHCID 498403282-carboxymethyl-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester

Product 1

HCID 666092272-{[(4-hydroxy-1-methyl-piperidin-4-ylmethyl)-carbamoyl]-methyl}-4-methyl-1H-pyrrole-3-carboxylic acid ethyl esterYield 149.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 2-carboxymethyl-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester (3.717 g, 17.62 mmol) in dichloromethane (91 ml) in an ice-water bath was added with 4-aminomethyl-1-methyl-piperidin-4-ol (4 g, 19.38 mmol), N,N′-dimethylformamide (9.1 ml), N-ethyl-N′-(dimethylaminopropyl)-carbodiimide hydrochloride (8.751 g, 45.6 mmol) and 1-hydroxybenzotriazol (3.577 g, 26.5 mmol). Upon completion of the addition, the resulting mixture was stirred at room temperature overnight. The mixture was added with ice to quench the reaction, and washed with saturated potassium carbonate solution (10 ml×3) with brine (50 ml×3) The resulting mixture was partitioned and the organic phase was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 2-{[(4-hydroxy-1-methyl-piperidin-4-ylmethyl)-carbamoyl]-methyl}-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester (8.891 g) as a brown oil, which was used as such.

Workup

  1. additionUpon completion of the addition
  2. additionThe mixture was added with ice
  3. customto quench
  4. customthe reaction
  5. washwashed with saturated potassium carbonate solution (10 ml×3) with brine (50 ml×3) The resulting mixture
  6. customwas partitioned
  7. dry with materialthe organic phase was dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-640a441b42784464af8cbeafa3e7005d
Source dataset
uspto-grants-2013_01
Patent number
US08362251B2

Reaction notes

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