Dimethylformamide → HCID 22311913, compound

Participants

Reaction Steps

As a typical example of this convergent solution-phase method, Compound 1 may be synthesized as described in Scheme AA. Thus, treatment of 5-nitrobenzimidazolone AAI with 2,6-diCl-Bn-Br in the presence of NaH in DMF afforded two regioisomers AA2a and AA3a (ca. 1:1 ratio), which were then separated by flash column. A small amount of bis-alkylated product was also obtained. The isolated AA3a was further alkylated with 2-chloroethylpyrrolidine by using NaH as a base in DMF to give the di-alkylated product, which was then subjected to nitro reduction with Me2NNH2/FeCl3 to provide aminobenzimidazolone intermediate AA4. Coupling of N-α-Fmoc-N-γ-Boc-diaminobutyric acid (AA5) with benzyl amine in the presence of DCC and HOBt was followed by de-protection of the Fmoc group with diethylamine. The resulting intermediate was coupled with Fmoc-3,4-diF-Phe-OH using DIC/HOBt and treated with diethylamine to give dipeptide amine AA6. Urea formation between the dipeptide amine AA6 and aminobenzimidazolone intermediate AA4 in the presence of 4-nitrophenylchloroformate was followed by de-protection of the Boc group with TFA to afford the target compound 1.

Provenance & Evidence