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

HRID 73256Notes

Reaction equation

HRID 73256 reaction equation
Cl.[CH2:2]([N:4]=C=NCCCN(C)C)[CH3:3].[CH2:13]([N:15]([CH2:18][CH3:19])[CH2:16][CH3:17])[CH3:14].[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].ON1C2C=CC=CC=2N=N1.[CH3:42][N:43]([CH:45]=[O:46])C>O>[CH2:13]([N:15]1[CH2:18][CH2:19][CH2:17][CH:16]1[CH2:42][NH:43][C:45](=[O:46])[CH:2]([NH:4][C:28]([C:24]1[C:23]([CH3:31])=[C:22]([CH:20]=[O:21])[NH:26][C:25]=1[CH3:27])=[O:30])[CH3:3])[CH3:14]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 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 86659147N-{1-[(1-ethylpyrrolidin-2-yl)methylamino]-1-oxoprop-2-yl}-5-formyl-2,4-dimethyl-1H-pyrrole-3-formamideYield 49.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

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 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 (1.59 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 0.696 g (2.0 mmol) of N-{1-[(1-ethylpyrrolidin-2-yl)methylamino]-1-oxoprop-2-yl}-5-formyl-2,4-dimethyl-1H-pyrrole-3-formamide. Yield 49.8%. 1HNMR (DMSO-d6) δ 10.83 (s, br, 1H, NH), 9.75 (s, 1H), 7.72 (m, br, 1H, CONHCH2), 7.70 (m, br, 1H, CONHCH2), 4.71 (m. 1H), 3.07-3.03 (m, 2H), 2.85 (m, 1H), 2.49-2.46 (m, 2H), 2.37-2.31 (m, 3H), 2.30 (m, 2H), 2.14-2.09 (m, 3H), 1.68-1.64 (m, 2H), 1.56-1.54 (m, 2H), 1.48-1.41 (d, 3H), 1.07-1.04 (m, 3H).

Workup

  1. stirringstirred for 1.5 hrs
  2. customthe oily residue obtained in the above step (1.59 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-b900532639e5493098c944788deffb4f
Source dataset
uspto-grants-2014_09
Patent number
US08829039B2

Reaction notes

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