Solid-phase synthesis of 7-acylamino-1,4-benzodiazepine-2,5-diones
Ettmayer, P; Chloupek, S; Weigand, K
| HERO ID | 3539782 |
|---|---|
| In Press | No |
| Year | 2003 |
| Title | Solid-phase synthesis of 7-acylamino-1,4-benzodiazepine-2,5-diones |
| Authors | Ettmayer, P; Chloupek, S; Weigand, K |
| Journal | Journal of Combinatorial Chemistry |
| Volume | 5 |
| Issue | 3 |
| Page Numbers | 253-259 |
| Abstract | A method for the synthesis of polymer-bound 7-acylamino-benzodiazepine-2,5-diones is described. The amino group of an alpha-amino acid is linked to polystyrene or TentaGel resin via reductive amination of polymer-bound 4-alkoxy-2,6-dimethoxybenzaldehyde. Acylation with unprotected 5-nitroanthranilic acid is followed by base-catalyzed ring closure. Reduction of the nitro group yields enantiomerically pure 7-aminobenzodiazepin-2,5-dione attached via the N-4 atom to the resin. Acylation of the amino group on the aromatic ring with acid chlorides in N-methylpyrrolidone (no DMF, no base!) followed by cleavage from the resin using TFA/Me(2)S/water (90:5:5) provides the acylated benzodiazepinones in 52-69% (PS resin) and 41-48% (TG resin) yield (based on the theoretical loading) and >70% purity (HPLC, 210 nm). Using Fmoc-protected tyrosine fluoride in NMP gives the amino acid-coupled benzodiazepinones in 24% (PS resin) and 31% (TG resin) yield. |
| Doi | 10.1021/cc020100w |
| Pmid | 12739941 |
| Wosid | WOS:000185911100012 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Journal: ISSN: |
| Is Public | Yes |
| Language Text | English |