Water → HCID 86659148, compound

HRID 73257Notes

Reaction equation

HRID 73257 reaction equation
Cl.C(N=[C:5]=[N:6][CH2:7][CH2:8][CH2:9][N:10]([CH3:12])[CH3:11])C.C([N:15]([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].ON1[C:37]2C=CC=C[C:36]=2N=N1.[OH2:42]>CN(C=O)C>[CH3:12][N:10]1[CH2:11][CH2:37][CH2:36][CH:9]1[CH2:8][CH2:7][NH:6][C:5](=[O:42])[CH:18]([NH:15][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 86659148HCID 86659148, compoundYield 55.2%

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 added to DMF (10 mL) with stirring at about 0° C. and stirred for 1.5 hrs, and the compound 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 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 0.768 g (2.21 mmol) of N-{1-[2-(1-methylpyrrolidin-2-yl)ethylamino]-1-oxoprop-2-yl}-5-formyl-2,4-dimethyl-1H-pyrrole-3-formamide. Yield 55.2%. 1HNMR (DMSO-d6) δ 10.83 (s, br, 1H, NH), 9.75 (s, 1H), 7.78 (m, br, 1H, CONHCH2), 7.77 (m, br, 1H, CONHCH2), 4.71 (m, 1H), 3.12-3.10 (m, 2H), 2.86 (m, 1H), 2.37-2.31 (m, 3H), 2.30-2.22 (m, 2H), 2.26-2.20 (s, 3H), 2.12-2.08 (m, 3H), 1.68-1.64 (m, 2H), 1.61-1.53 (m, 2H), 1.56-1.54 (m, 2H), 1.48-1.41 (d, 3H).

Workup

  1. stirringstirred for 1.5 hrs
  2. customthe compound 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 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-a9841764bad3402982379c57180bdb56
Source dataset
uspto-grants-2014_09
Patent number
US08829039B2

Reaction notes

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