4-Nitrobenzaldehyde → HCID 69953773, compound

Participants

Reaction Steps

A mixture of L-proline (20 mmol), 4-nitrobenzaldehyde (20 mmol) and N-butylmaleimide (20 mmol) was heated to 80° C. in DMF (20 ml) for 24 hours. The solvent was removed in a high vacuum and the residue was separated chromatographically over silica gel (eluent hexane:ethyl acetate=1:1+1% triethylamine). (3aRS, 4SR,8aRS,8bSR)-2-Butyl-4-(4-nitro-phenyl)-hexahydro-pyrrolo[3,4-a]pyrrolizine-1,3-dione was obtained in 32% yield as a yellow solid (Rf =0.35). This product in 50 ml of ethanol was treated with 200 mg of 10% palladium on charcoal and reduced under hydrogen within 8 hours. After filtration of the catalyst and removal of the solvent in a vacuum (3aRS,4SR,8aRS,8bSR)-4-(4-amino-phenyl)-2-butyl-hexahydro-pyrrolo[3,4-a]pyrrolizine-1,3-dione was obtained as a pale yellow oil (Rf =0.23). 120 mg of this crude product were treated with 80 mg of 3,5-dimethyl-pyrazolyl-1-carboximidamidinium nitrate in 20 ml of DMF and heated at 80° C. for 48 hours. After removing the solvent in a vacuum the material remaining was separated on a RP-18 chromatography column with a water/methanol gradient. (3aRS,4SR,8aRS, 8bSR)-N-[4-(2-Butyl-1,3-dioxo-decahydro-pyrrolo[3,4-a]pyrrolizin-4-yl)-phenyl]-guanidinium nitrate was obtained in 12% yield as a pale yellow oil. ISP-MS: 483.4 ([M+H]+, 100).

Provenance & Evidence