3-[(2,5-Dioxopyrrolidin-1-yl)oxy]-3-oxopropanenitrile → HCID 67123537, compound

HRID 1887015Notes

Reaction equation

HRID 1887015 reaction equation
Cl.[O:2]=[C:3]1[NH:11][C:10]2[C:5](=[N:6][C:7]([C:12]3[CH:13]=[N:14][N:15]4[CH:20]=[CH:19][C:18]([C:21]#[N:22])=[CH:17][C:16]=34)=[N:8][CH:9]=2)[N:4]1[C@H:23]1[CH2:28][CH2:27][CH2:26][NH:25][CH2:24]1.[C:29]([CH2:31][C:32](ON1C(=O)CCC1=O)=[O:33])#[N:30]>CN(C=O)C>[C:29]([CH2:31][C:32]([N:25]1[CH2:26][CH2:27][CH2:28][C@H:23]([N:4]2[C:3](=[O:2])[NH:11][C:10]3[C:5]2=[N:6][C:7]([C:12]2[CH:13]=[N:14][N:15]4[CH:20]=[CH:19][C:18]([C:21]#[N:22])=[CH:17][C:16]=24)=[N:8][CH:9]=3)[CH2:24]1)=[O:33])#[N:30]

Participants

4

Reactant 2

HCID 534158963-[(2,5-Dioxopyrrolidin-1-yl)oxy]-3-oxopropanenitrileHCID 67123442HCID 67123442, compound

Product 1

HCID 67123537HCID 67123537, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the compound obtained in example 6 (45 mg, 0.095 mmol) in anhydrous DMF (3 mL), 2,5-dioxopyrrolidin-1-yl 2-cyanoacetate (69 mg, 0.38 mmol) and anhydrous TEA (0.09 mL, 0.665 mmol) were added. The reaction mixture was stirred at room temperature for 18 h, and the solvent was concentrated off. It was quenched with saturated NaHCO3 aqueous solution (15 mL) and extracted with EtOAc (3×15 mL). The combined organic phases were dried over anhydrous Mg2SO4, filtered and concentrated. The crude residue was flash chromatographed on a silica gel flash system (ISCO Rf) using hexanes/acetone mixtures of increasing polarity as eluent to afford 11.7 mg of the desired compound (29% yield).

Workup

  1. concentrationthe solvent was concentrated off
  2. customIt was quenched with saturated NaHCO3 aqueous solution (15 mL)
  3. extractionextracted with EtOAc (3×15 mL)
  4. dry with materialThe combined organic phases were dried over anhydrous Mg2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customchromatographed on a silica gel flash system (ISCO Rf)
  8. temperatureof increasing polarity as eluent

Sources & evidence

ORD record
ord-5644b0f2977747f5b74b1d44c1f770f9
Source dataset
uspto-grants-2013_08
Patent number
US08501735B2

Reaction notes

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