Dimethylformamide → HCID 22311913, compound
Reaction equation
CCCC[C@H]1C(=O)O[C@H](C)[C@H](NC(C2[CH:25]=[CH:24][CH:23]=[C:22]([NH:26]C=O)[C:21]=2O)=O)C(=O)O[C@@H](C)[C@@H]1OC(C(CC)C)=O.ClCC[N:41]1CCCC1.[H-].[Na+].C[N:49]([CH:51]=[O:52])[CH3:50]>>[NH2:26][C:22]1[C:21]2[C:50](=[N:49][C:51](=[O:52])[N:41]=2)[CH:25]=[CH:24][CH:23]=1Participants
Procedure
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.
Workup
- customand AA3a (ca. 1:1 ratio), which were then separated by flash column
- customA small amount of bis-alkylated product was also obtained
- customto give the di-alkylated product, which
Sources & evidence
- ORD record
- ord-e29edc39a0044b43bf408e7d6cad9fc8
- Source dataset
- uspto-grants-2003_10
- Patent number
- US06630451B1
Reaction notes
Loading…