1-Methylpyrrolidine → methyl 4-ethyl-2-formyl-5-thien-2-yl-1H-pyrrole-3-carboxylate

HRID 1785006Notes

Reaction equation

HRID 1785006 reaction equation
[CH2:1]([C:3]1[C:4]([C:11]([O:13][CH3:14])=[O:12])=[C:5]([CH:9]=[O:10])[NH:6][C:7]=1I)[CH3:2].Br[Zn][C:17]1[S:18][CH:19]=[CH:20][CH:21]=1.CN1CCCC1>C1COCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH2:1]([C:3]1[C:4]([C:11]([O:13][CH3:14])=[O:12])=[C:5]([CH:9]=[O:10])[NH:6][C:7]=1[C:17]1[S:18][CH:19]=[CH:20][CH:21]=1)[CH3:2]

Participants

6

Reactant 3

HCID 84541-MethylpyrrolidineHCID 11278208Methyl 4-ethyl-2-formyl-5-iodo-1H-pyrrole-3-carboxylateHCID 178419762HCID 178419762, compound

Product 1

HCID 11380023methyl 4-ethyl-2-formyl-5-thien-2-yl-1H-pyrrole-3-carboxylate

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

Methyl 4-ethyl-2-formyl-5-iodo-1H-pyrrole-3-carboxylate was obtained following the procedures described in Example 3. To a solution of methyl 4-ethyl-2-formyl-5-iodo-1H-pyrrole-3-carboxylate (0.123 g, 0.40 mmol) and bromo(thien-2-yl)zinc (0.1374 g, 0.60 mmol) in THF (2.0 mL) was added Pd(Pt-Bu3)2 (0.0123 g, 0.02 mmol) and N-methylpyrrolidine (2.0 mL). The reaction was deoxygenated by bubbling argon through the solution prior to being heated to 100° C. and refluxed for 4 h under argon. After cooling to ambient temperature, the reaction was filtered through a pad of silica gel and concentrated. The resultant residue was dissolved in acetonitrile and purified by reverse phase HPLC. Proton NMR for the product was consistent with the title compound. 1H NMR (500 MHz, CDCl3) δ 10.14 (s, 1H); 7.42 (d, J=5.1 Hz, 1H); 7.24 (d, J=3.7 Hz, 1H); 7.14 (dd, J=3.7, 4.7 Hz, 1H); 3.94 (s, 3H); 2.94 (q, J=7.4 Hz, 2H); 1.24 (t, J=7.4 Hz, 3H). HRMS (ES) exact mass calculated C13H14NO3S (M+H): 264.0689. Found 264.0688

Workup

  1. customThe reaction was deoxygenated
  2. customby bubbling argon through the solution
  3. temperaturerefluxed for 4 h under argon
  4. temperatureAfter cooling to ambient temperature
  5. filtrationthe reaction was filtered through a pad of silica gel
  6. concentrationconcentrated
  7. dissolutionThe resultant residue was dissolved in acetonitrile
  8. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-f56d8cdb74bd43b89e7e5dfe834e5229
Source dataset
uspto-grants-2009_03
Patent number
US07504429B2

Reaction notes

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