反应详情

A mixture of {1-[4-(2-bromo-2-phenyl-acetyl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester [Int-1-A] (0.87 g, 2.0 mmol), 2-amino-5-ethoxypyridine (0.54 g, 3.9 mmol, 2 equiv) and powdered activated 3A sieves (10 g) in ethanol (7.3 mL) was heated for 5 h at the reflux temperature with monitoring by UPLC-MS. The resulting solution was separated between CH2Cl2 (25 mL) and an saturated aqueous NaHCO3 solution (25 mL). The organic phase was washed with a saturated aqueous NaCl solution (25 mL), dried (Na2SO4 anh), and concentrated under reduced pressure. The remaining material was purified using MPLC (Biotage Isolera; 25 g SNAP cartridge: 100% hexane for 1.5 min., gradient to 80% hexane/20% EtOAc over 2.2 min., gradient to 70% hexane/30% EtOAc over 10.6 min., 70% hexane/30% EtOAc for 2.8 min., gradient to 65% hexane/35% EtOAc over 2.2 min., 65% hexane/35% EtOAc for 4.8 min.) to give {1-[4-(6-ethoxy-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (0.26 g, 28%):

1. temperaturewas heated for 5 h at the reflux temperature with monitoring by UPLC-MS
2. customThe resulting solution was separated between CH2Cl2 (25 mL)
3. washThe organic phase was washed with a saturated aqueous NaCl solution (25 mL)
4. dry with materialdried (Na2SO4 anh)
5. concentrationconcentrated under reduced pressure
6. customThe remaining material was purified
7. customMPLC (Biotage Isolera; 25 g SNAP cartridge: 100% hexane for 1.5 min., gradient to 80% hexane/20% EtOAc over 2.2 min., gradient to 70% hexane/30% EtOAc over 10.6 min., 70% hexane/30% EtOAc for 2.8 min., gradient to 65% hexane/35% EtOAc over 2.2 min., 65% hexane/35% EtOAc for 4.8 min.)