2-[3-(S)-Benzyloxycarbonylamino-2-oxo-pyrrolidin-1-ylmethyl)-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester → 2-[3-(S)-Amino-2-oxo-pyrrolidin-1-ylmethyl)-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester

HRID 651672Notes

Reaction equation

HRID 651672 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[CH:15]=[CH:14][N:13]=[CH:12][C:11]=2[CH:10]=[C:9]1[CH2:17][N:18]1[CH2:22][CH2:21][C@H:20]([NH:23]C(OCC2C=CC=CC=2)=O)[C:19]1=[O:34])=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(O)=O.CO.O.[Pd]>[C:1]([O:5][C:6]([N:8]1[C:16]2[CH:15]=[CH:14][N:13]=[CH:12][C:11]=2[CH:10]=[C:9]1[CH2:17][N:18]1[CH2:22][CH2:21][C@H:20]([NH2:23])[C:19]1=[O:34])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 1

HCID 697099132-[3-(S)-Benzyloxycarbonylamino-2-oxo-pyrrolidin-1-ylmethyl)-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester

Product 1

HCID 543682692-[3-(S)-Amino-2-oxo-pyrrolidin-1-ylmethyl)-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 962WaterSolventHCID 18963719Formic acid methanolSolvent

Procedure

2-[3-(S)-Benzyloxycarbonylamino-2-oxo-pyrrolidin-1-ylmethyl)-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester (2.8 g, 6.0 mmol) in HCO2H/MeOH (30 mL, 4.4% solution) is quickly added via cannula to a solution of palladium black (2.0 g, 18.8 mmol) in water (1 ml,). After ca. 40 min the catalyst is filtered through Celite and basified with saturated sodium bicarbonate solution. The filtrate is concentrated in vacuo to remove methanol then the resulting solution is extracted with methylene chloride. The organic layer is washed with brine, dried over MgSO4, filtered and concentrated to dryness. The resulting white solid can be used in the subsequent step without further purification. The title compound was purified in the following manner to prepare a focused sulfonamide library. The crude solid was purified by RP-HPLC eluting with a gradient of 10% CH3CN/H2O (0.1% TFA) to 100% CH3CN. The appropriate fractions are combined and neutralized with saturated sodium bicarbonate solution then concentrated to remove CH3CN. The aqueous layer is extracted with methylene chloride (×4) and the organic layers are washed with brine, dried over MgSO4, filtered and concentrated to give the title compound as a white solid.

Workup

  1. filtrationAfter ca. 40 min the catalyst is filtered through Celite
  2. concentrationThe filtrate is concentrated in vacuo
  3. customto remove methanol
  4. extractionthe resulting solution is extracted with methylene chloride
  5. washThe organic layer is washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customThe resulting white solid can be used in the subsequent step without further purification
  10. customThe title compound was purified in the following manner
  11. customto prepare a focused sulfonamide library
  12. customThe crude solid was purified by RP-HPLC
  13. washeluting with a gradient of 10% CH3CN/H2O (0.1% TFA) to 100% CH3CN
  14. concentrationthen concentrated
  15. customto remove CH3CN
  16. extractionThe aqueous layer is extracted with methylene chloride (×4)
  17. washthe organic layers are washed with brine
  18. dry with materialdried over MgSO4
  19. filtrationfiltered
  20. concentrationconcentrated

Sources & evidence

ORD record
ord-dab408d85e7b46bcb22ea9015f292305
Source dataset
uspto-grants-2001_08
Patent number
US06281227B1

Reaction notes

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