反应详情

To a solution of methyl 5-(4-methoxyphenyl)-2-({[(trichloroacetyl)amino]carbonyl}amino)thiophene-3-carboxylate (1.36 g, 3 mmol) in anhydrous THF (20 mL) was added a solution of [Me2Al-3-Boc-(S)-3-aminohomopiperidine] in THF (preformed by the careful addition of Me3Al (2.0 M in hexanes, 3.0 mL, 6.0 mmol) to a solution of (S)-3-amino-azepane-1-carboxylic acid tert-butyl ester in 10 nL of THF at −78° C. followed by warming to room temperature under nitrogen and stirring for an additional 15 min.). The resulting deep yellow/orange solution was stirred overnight at room temperature. The reaction mixture was cooled with ice and a 10% aqueous solution of Rochelle's salt was added slowly to quench the reaction. The resulting biphasic solution was warmed to room temperature and stirred for an additional 1 h. The mixture was diluted with EtOAc and H2O, the aqueous layer was extracted with EtOAc (3×) and the combined organic extracts were washed with H2O, brine and dried (Na2SO4). Evaporation gave a pale orange solid. Purification by ISCO MPLC (SiO2, 60-80% EtOAc/hexanes) gave 0.9 g (62%) of the title compound as a white solid. 1H NMR (d6-DMSO, δ 11.0, s, 1H, δ 7.95, d, 0.5H, δ 7.81, d, 0.5H, δ 7.65, s, 0.5H; δ 7.56, s, 0.5H; δ 7.46, d, 2H; δ 6.97, d, 2H; δ 6.96, br s, 2H; δ 4.19, m, 0.5H; δ 4.11, m, 0.5H; δ 3.77, m, 3H; δ 3.65, m, 1H; δ 3.48, m, 1H; δ 3.20, m, 2H; δ 1.75, m, 3H; δ 1.58, m, 2H; δ 1.42, s, 4.5H; δ 1.39, m, 1H; δ 1.36, s, 4.5H), LC/MS (APCI, ES, M+H=489).

1. stirringThe resulting deep yellow/orange solution was stirred overnight at room temperature
2. temperatureThe reaction mixture was cooled with ice
3. customto quench
4. customthe reaction
5. temperatureThe resulting biphasic solution was warmed to room temperature
6. stirringstirred for an additional 1 h
7. extractionthe aqueous layer was extracted with EtOAc (3×)
8. washthe combined organic extracts were washed with H2O, brine
9. dry with materialdried (Na2SO4)
10. customEvaporation
11. customgave a pale orange solid
12. customPurification by ISCO MPLC (SiO2, 60-80% EtOAc/hexanes)