Water → N-{2-[(1-ethylpyrrolidin-2-yl)methylamino]-2-oxoethyl}-5-formyl-2,4-dimethyl-1H-pyrrole-3-formamide

HRID 73255Notes

Reaction equation

HRID 73255 reaction equation
Cl.C(N=C=NC[CH2:8][CH2:9][N:10](C)C)C.C(N([CH2:18][CH3:19])CC)C.[CH:20]([C:22]1[NH:26][C:25]([CH3:27])=[C:24]([C:28]([OH:30])=O)[C:23]=1[CH3:31])=[O:21].O[N:33]1[C:37]2[CH:38]=[CH:39][CH:40]=C[C:36]=2[N:35]=N1.[OH2:42]>CN(C=O)C>[CH2:18]([N:33]1[CH2:40][CH2:39][CH2:38][CH:37]1[CH2:36][NH:35][C:8](=[O:42])[CH2:9][NH:10][C:28]([C:24]1[C:23]([CH3:31])=[C:22]([CH:20]=[O:21])[NH:26][C:25]=1[CH3:27])=[O:30])[CH3:19]

Participants

7

Reactant 5

HCID 962Water2×HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 110737925-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic Acid

Product 1

HCID 86659146N-{2-[(1-ethylpyrrolidin-2-yl)methylamino]-2-oxoethyl}-5-formyl-2,4-dimethyl-1H-pyrrole-3-formamideYield 58.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

1-Ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (1.074 g, 5.6 mmol), triethylamine (1.12 mL, 8 mmol), 5-formyl-2,4-dimethyl-1H-pyrrole-3-formic acid (0.668 g, 4 mmol) and 1-hydroxybenzotriazole (0.756 g, 5.6 mmol) were sequentially added to DMF (10 mL) with stirring at about 0° C. and stirred for 1.5 hrs, and the oily residue obtained in the above step (1.48 g, 8 mmol) was added. The reaction was stirred at room temperature until completion was indicated by thin layer chromatography (TLC). 1.2 mL of water and 1 mL of saturated salt water were added, and the mixture was extracted with organic solvents (10% methanol/dichloromethane) (25 mL×3), the combined organic phase was washed with saturated salt water (25 mL×3), dried over anhydrous Na2SO4, and the solvent was distilled off under reduced pressure. The residue was then chromatographed (silica gel column chromatography, eluent: methanol:ethyl acetate=1:2) to give 0.786 g (2.35 mmol) of N-{2-[(1-ethylpyrrolidin-2-yl)methylamino]-2-oxoethyl}-5-formyl-2,4-dimethyl-1H-pyrrole-3-formamide. Yield 58.8%. 1HNMR (DMSO-d6) δ10.83 (s, br, H, NH), 9.75 (s, 1H), 7.74 (m, br, 1H, CONHCH2), 7.51 (m, br, 1H, CONHCH2), 3.85-3.83 (d, 2H), 3.07-3.03 (m, 2H), 2.85 (m, 1H), 2.49-2.46 (m, 2H), 2.32-2.30 (m, 2H), 2.37-2.33 (m, 3H), 2.14-2.10 (m, 3H), 1.68-1.64 (m, 2H), 1.56-1.54 (m, 2H), 1.06-1.01 (m, 3H).

Workup

  1. stirringstirred for 1.5 hrs
  2. customthe oily residue obtained in the above step (1.48 g, 8 mmol)
  3. additionwas added
  4. stirringThe reaction was stirred at room temperature until completion
  5. extractionthe mixture was extracted with organic solvents (10% methanol/dichloromethane) (25 mL×3)
  6. washthe combined organic phase was washed with saturated salt water (25 mL×3)
  7. dry with materialdried over anhydrous Na2SO4
  8. distillationthe solvent was distilled off under reduced pressure
  9. customThe residue was then chromatographed (silica gel column chromatography, eluent: methanol:ethyl acetate=1:2)

Sources & evidence

ORD record
ord-2e5942fe3a914f2889c8064a71ead8d9
Source dataset
uspto-grants-2014_09
Patent number
US08829039B2

Reaction notes

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