Dicyclohexylcarbodiimide → N-(2-(diethylamino)ethyl)-5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxamide

HRID 1888975Notes

Reaction equation

HRID 1888975 reaction equation
[CH:1]([C:3]1[NH:7][C:6]([CH3:8])=[C:5]([C:9]([OH:11])=O)[C:4]=1[CH3:12])=[O:2].C1(N=C=NC2CCCCC2)CCCCC1.ON1C2C=CC=CC=2N=N1.[CH2:38]([N:40]([CH2:44][CH3:45])[CH2:41][CH2:42][NH2:43])[CH3:39]>O1CCCC1>[CH2:38]([N:40]([CH2:44][CH3:45])[CH2:41][CH2:42][NH:43][C:9]([C:5]1[C:4]([CH3:12])=[C:3]([CH:1]=[O:2])[NH:7][C:6]=1[CH3:8])=[O:11])[CH3:39]

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 60993N,N-DiethylethylenediamineHCID 757711-HydroxybenzotriazoleHCID 110737925-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic Acid

Product 1

HCID 20761785N-(2-(diethylamino)ethyl)-5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
2.5 °C

Procedure

Into a 10-L four necked round-bottomed flask equipped with a mechanical stirrer, a thermometer pocket, addition funnel and an air condenser were charged 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (0.25 Kg; 1.5 mole), tetrahydrofuran (3.5 L), dicyclohexyl carbodimide (0.432 Kg), 1-hydroxy benzotriazole (0.306 Kg) and stirred well for 30 minutes. To this solution, a premixed solution of TEA (0.42 L) in tetrahydrofuran (1.25 L) and 2-diethylaminoethyl amine (0.286 L; 2.04 mole) in tetrahydrofuran (1.25 L) were added successively at 25-30° C. After addition, the reaction mixture was stirred for 16 hours at 25-30° C. and the byproduct generated was removed by filtration through filtration funnel. The solvent was removed by distillation under diminished pressure. The resulting product was suspended in DM water and the pH of the slurry adjusted to 12-13 with aqueous NaOH solution. After pH adjustment, the product was extracted with ethyl acetate and washed successively organic layer with aqueous NaHCO3, saturated solution of NaCl and DM water. Organic layer was separated and ¾th of the solvent distilled under diminished pressure. The product was cooled to 0-5° C. and stirred for 2 hours, filtered and washed with chilled ethyl acetate (70 mL). The product was dried at 60° C.

Workup

  1. additiona thermometer pocket, addition funnel and an air condenser
  2. additionAfter addition
  3. stirringthe reaction mixture was stirred for 16 hours at 25-30° C.
  4. customthe byproduct generated was removed by filtration through filtration funnel
  5. customThe solvent was removed by distillation under diminished pressure
  6. extractionAfter pH adjustment, the product was extracted with ethyl acetate
  7. washwashed successively organic layer with aqueous NaHCO3, saturated solution of NaCl and DM water
  8. customOrganic layer was separated
  9. distillation¾th of the solvent distilled under diminished pressure
  10. stirringstirred for 2 hours
  11. filtrationfiltered
  12. washwashed with chilled ethyl acetate (70 mL)
  13. customThe product was dried at 60° C.

Sources & evidence

ORD record
ord-b02d16fa7596434b9c8938e008cbff37
Source dataset
uspto-grants-2013_08
Patent number
US08501962B2

Reaction notes

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