Methyl 6-(2,2-dimethylpropionylamino)-2-nitro-3-(2-oxopyrrolidin-1-yl)-benzoate → methyl 6-(2,2-dimethylpropionylamino)-2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazole-5-carboxylate

HRID 715987Notes

Reaction equation

HRID 715987 reaction equation
[CH3:1][C:2]([CH3:26])([CH3:25])[C:3]([NH:5][C:6]1[C:11]([C:12]([O:14][CH3:15])=[O:13])=[C:10]([N+:16]([O-])=O)[C:9]([N:19]2[CH2:23][CH2:22][CH2:21][C:20]2=O)=[CH:8][CH:7]=1)=[O:4]>C(O)(=O)C.[Fe]>[CH3:1][C:2]([CH3:26])([CH3:25])[C:3]([NH:5][C:6]1[C:11]([C:12]([O:14][CH3:15])=[O:13])=[C:10]2[N:16]=[C:20]3[CH2:21][CH2:22][CH2:23][N:19]3[C:9]2=[CH:8][CH:7]=1)=[O:4]

Participants

4

Reactant 1

HCID 70982623Methyl 6-(2,2-dimethylpropionylamino)-2-nitro-3-(2-oxopyrrolidin-1-yl)-benzoate2×

Product 1

HCID 70983330methyl 6-(2,2-dimethylpropionylamino)-2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazole-5-carboxylateYield 79.7%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
115 °C

Procedure

A mixture of methyl 6-(2,2-dimethylpropionylamino)-2-nitro-3-(2-oxopyrrolidin-1-yl)-benzoate (Intermediate 57, 0.89 g), and iron powder (1.37 g) in acetic acid (25 mL) was stirred and heated at 115° C. for 2.5 hours. After cooling, the mixture was concentrated in vacuo and the residue was dissolved in ethyl acetate and 2M sodium hydroxide solution and filtered through celite. The organic phase was dried (Na2SO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 50-100%. The product was repurified by chromatography on silica, eluting with a mixture of methanol and ethyl acetate with a gradient of 0-10% to give methyl 6-(2,2-dimethylpropionylamino)-2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazole-5-carboxylate (0.616 g) as an off-white solid.

Workup

  1. temperatureAfter cooling
  2. concentrationthe mixture was concentrated in vacuo
  3. dissolutionthe residue was dissolved in ethyl acetate
  4. filtration2M sodium hydroxide solution and filtered through celite
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was purified by chromatography on silica
  9. washeluting with a mixture of ethyl acetate and cyclohexane with a gradient of 50-100%
  10. customThe product was repurified by chromatography on silica
  11. washeluting with a mixture of methanol and ethyl acetate with a gradient of 0-10%

Sources & evidence

ORD record
ord-e2d4b102ca7d4390bc7dcbfc2dac7315
Source dataset
uspto-grants-2015_11
Patent number
US09187494B2

Reaction notes

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