Triethylamine → Methyl 3-amino-4-cyano-1H-pyrrole-2-carboxylate

HRID 490223Notes

Reaction equation

HRID 490223 reaction equation
[NH2:1][CH:2]([C:7]([O:9][CH3:10])=[O:8])[C:3](OC)=O.C(O[CH:14]=[C:15](C#N)[C:16]#[N:17])C.C([N:22](CC)CC)C.C[O-].[Na+].CO>CO.C(O)(=O)C>[NH2:22][C:3]1[C:15]([C:16]#[N:17])=[CH:14][NH:1][C:2]=1[C:7]([O:9][CH3:10])=[O:8]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 671522-(Ethoxymethylene)propanedinitrileHCID 437601Dimethyl aminomalonate hydrochlorideHCID 23694274Sodium methanolate methanol

Product 1

HCID 23033051Methyl 3-amino-4-cyano-1H-pyrrole-2-carboxylateYield 61%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent3×

Procedure

After dissolving dimethyl 2-aminomalonate (25.0 g) in methanol (300 mL), a solution of ethoxymethylene-malononitrile (16.6 g) and triethylamine (15.1 g) in methanol (50 mL) was added. The reaction mixture was stirred at room temperature for 18 hours and then cooled to 0° C., and a mixed solution of 28% sodium methoxide/methanol (31.5 g) and methanol (50 mL) was added dropwise thereto over a period of 10 minutes. The reaction mixture was stirred at room temperature for 49 hours and then cooled to 0° C., and acetic acid (10.3 g) was added. The solvent was distilled off under reduced pressure, ethyl acetate (200 mL) and water (200 mL) were added to the residue and extraction was performed with ethyl acetate. A saturated aqueous sodium bicarbonate solution was added to the organic layer until it exhibited a pH of 8, and extraction was performed with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/1) to obtain the title compound (13.7 g, 61%) as a brown solid. The NMR and ESI/MS data for this compound are shown below.

Workup

  1. temperaturecooled to 0° C.
  2. waitover a period of 10 minutes
  3. stirringThe reaction mixture was stirred at room temperature for 49 hours
  4. temperaturecooled to 0° C.
  5. distillationThe solvent was distilled off under reduced pressure, ethyl acetate (200 mL) and water (200 mL)
  6. additionwere added to the residue and extraction
  7. additionA saturated aqueous sodium bicarbonate solution was added to the organic layer until it
  8. extractiona pH of 8, and extraction
  9. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  10. distillationthe solvent was distilled off under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/1)

Sources & evidence

ORD record
ord-4643258bf45144df90f2c48ffed52d5d
Source dataset
uspto-grants-2009_05
Patent number
US07528140B2

Reaction notes

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