反应详情

温度

0 °C

To generate the acid chloride, oxalyl chloride (70 μL, 0.83 mmol) and DMF (1 drop) were added to a suspension of 3-methyl-1,2-oxazole-4-carboxylic acid (50 mg, 0.40 mmol) in CH2Cl2 (0.5 mL) at 0° C. The suspension was allowed to stir for 15 min at 0° C., followed by 2 h at room temperature. The resulting solution was concentrated in vacuo to give a brown oil that was suspended in n-hexanes (2×1 mL) and concentrated in vacuo. To a chilled (ice bath) suspension of the acid chloride (generated as above; 0.40 mmol) in pyridine (0.5 mL) and CH2Cl2 (0.5 mL) was added 4-(5-oxo-2,3-dihydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-10a(10H)-yl)benzonitrile (22 mg, <79 μmol) in pyridine (0.5 mL). The brown reaction mixture was warmed to room temperature and stirred for a further 64 h. Saturated aqueous NaHCO3 (25 mL) was then added and the mixture extracted with CH2Cl2 (3×25 mL). The organic fractions were combined, dried (MgSO4) and concentrated in vacuo to yield a residue that was purified using flash chromatography (Biotage SP4 12 g cartridge; 0-10% MeOH gradient in CH2Cl2) to give a mixture of products containing the desired product. The mixture was further purified using flash chromatography (Biotage SP4, 12 g cartridge, C18 phase, 20-40% acetonitrile gradient in water) to give 4-{1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-5-oxo-2,3-dihydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-10a(10H)-yl}benzonitrile (37) as a white solid (13 mg, yield 42%).

1. waitfollowed by 2 h at room temperature
2. concentrationThe resulting solution was concentrated in vacuo
3. customto give a brown oil that
4. concentrationconcentrated in vacuo
5. temperatureTo a chilled
6. temperatureThe brown reaction mixture was warmed to room temperature
7. stirringstirred for a further 64 h
8. extractionthe mixture extracted with CH2Cl2 (3×25 mL)
9. dry with materialdried (MgSO4)
10. concentrationconcentrated in vacuo
11. customto yield a residue that
12. customwas purified
13. customto give
14. additiona mixture of products