HCID 11348633, compound → HCID 11232774, compound

HRID 495215Notes

Reaction equation

HRID 495215 reaction equation
Br[Zn][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[N:4]=1.[CH2:11]([C:13]1[C:17](I)=[C:16]([CH:19]=[O:20])[NH:15][C:14]=1[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH3:12]>C1COCC1.CN1CCCC1.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>[CH2:11]([C:13]1[C:17]([C:3]2[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[N:4]=2)=[C:16]([CH:19]=[O:20])[NH:15][C:14]=1[C:21]([O:23][C:24]([CH3:25])([CH3:27])[CH3:26])=[O:22])[CH3:12]

Participants

6

Reactant 2

HCID 11348633HCID 11348633, compoundHCID 178491783HCID 178491783, compound

Product 1

HCID 11232774HCID 11232774, compound

Reagents, catalysts & solvents 3

HCID 178418851HCID 178418851, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 84541-MethylpyrrolidineSolvent

Conditions

Temperature
100 °C

Procedure

Tert-butyl 3-ethyl-5-formyl-4-iodo-1H-pyrrole-2-carboxylate was obtained following the procedures described in Example 1. To a solution of bromo(6-methoxypyridin-2-yl)zinc (0.076 g, 0.30 mmol) in THF (0.6 mL) and N-methylpyrrolidine (0.44 mL) under argon was added Pd(Pt-Bu3)2 (0.002 g, 0.0032 mmol) and tert-butyl 3-ethyl-5-formyl-4-iodo-1H-pyrrole-2-carboxylate (0.070 g, 0.20 mmol). The reaction was heated to 100° C. and refluxed for 20 h under argon. After cooling to ambient temperature, the reaction was filtered through a pad of silica gel and concentrated. The resultant residue purified by normal phase flash chromatography (5-15% ethyl acetate/hexanes). Proton NMR for the product was consistent with the title compound. 1H NMR (500 MHz, CDCl3) δ 9.86 (s, 1H); 7.66 (t, J=7.8 Hz, 1H); 7.02 (d, J=7.1 Hz, 1H); 6.76 (d, J=8.3 Hz, 1H); 3.95 (s, 3H); 2.90 (q, J=7.3 Hz, 2H); 1.61 (s, 9H); 1.23 (t, J=7.3 Hz, 3H). HRMS (ES) exact mass calculated for C18H23N2O4 (M+H+): 331.1656. Found 331.1656.

Workup

  1. temperaturerefluxed for 20 h under argon
  2. temperatureAfter cooling to ambient temperature
  3. filtrationthe reaction was filtered through a pad of silica gel
  4. concentrationconcentrated
  5. customThe resultant residue purified by normal phase flash chromatography (5-15% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-a0ed72fa4ab047d884153e23d11ae80c
Source dataset
uspto-grants-2009_05
Patent number
US07538231B2

Reaction notes

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