1-Hydroxybenzotriazole → N-[(1-ethylpyrrolidin-2-yl) methyl]-5-formyl-2,4-dimethyl-1H-pyrrole-3-formamide

HRID 73246

Reaction equation

HRID 73246 reaction equation
Cl.C(N=C=NCCCN(C)C)C.[CH:13]([C:15]1[NH:19][C:18]([CH3:20])=[C:17]([C:21]([OH:23])=O)[C:16]=1[CH3:24])=[O:14].ON1C2C=CC=CC=2N=N1.[CH2:35]([N:37]1[CH2:41][CH2:40][CH2:39][CH:38]1[CH2:42][NH2:43])[CH3:36]>O.CN(C=O)C.C(N(CC)CC)C>[CH2:35]([N:37]1[CH2:41][CH2:40][CH2:39][CH:38]1[CH2:42][NH:43][C:21]([C:17]1[C:16]([CH3:24])=[C:15]([CH:13]=[O:14])[NH:19][C:18]=1[CH3:20])=[O:23])[CH3:36]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 1172952-Aminomethyl-1-ethylpyrrolidineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 110737925-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic Acid

Product 1

HCID 86659136N-[(1-ethylpyrrolidin-2-yl) methyl]-5-formyl-2,4-dimethyl-1H-pyrrole-3-formamideYield 47.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

1-Ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (268.1 g, 1.4 mol), triethylamine (280.0 mL), 5-formyl-2,4-dimethyl-1H-pyrrole-3-formic acid (167.0 g, 1.0 mol) and 1-hydroxybenzotriazole (189.2 g, 1.4 mol) were added to DMF (500 mL) with stirring at about 0° C. and allowed to stir for 1.5 hrs, and then (1-ethylpyrrolidin-2-yl)methylamine (1.2 mol) was added. The reaction was stirred at room temperature until completion was indicated by thin layer chromatography (TLC). 120 mL of water and 100 mL of saturated salt water were added, and the mixture was extracted with 10% methanol/dichloromethane (300 mL×3). The combined organic phase was washed with saturated salt water (300 mL×3), dried over anhydrous Na2SO4, and the solvent was distilled off under reduced pressure. The residue was chromatographed on silica gel (eluted with methanol/ethyl acetate=1/1) to afford 131.86 g (476 mmol) of N-[(1-ethylpyrrolidin-2-yl) methyl]-5-formyl-2,4-dimethyl-1H-pyrrole-3-formamide as an off-white solid. Yield 47.6%, m.p. 166-169° C.

Workup

  1. stirringto stir for 1.5 hrs
  2. stirringThe reaction was stirred at room temperature until completion
  3. extractionthe mixture was extracted with 10% methanol/dichloromethane (300 mL×3)
  4. washThe combined organic phase was washed with saturated salt water (300 mL×3)
  5. dry with materialdried over anhydrous Na2SO4
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe residue was chromatographed on silica gel (eluted with methanol/ethyl acetate=1/1)

Sources & evidence

ORD record
ord-130b3f69955b4e078fca89047b15a363
Source dataset
uspto-grants-2014_09
Patent number
US08829039B2

Linked notes

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