反应详情

To a solution of tert-butyl (6-methoxypyridin-3-yl)carbamate (5.98 g, 26.7 mmol) in tetrahydrofuran (THF) (20 mL) at −78° C. under N2 was added n-BuLi (2.5M in hexanes) (10.66 mL, 26.7 mmol). The mixture was allowed to warm up to RT and stirred for 20 min, to the mixture was added 1-{[(3S,5S)-5-methyl-1-oxaspiro[2.5]oct-5-yl]methyl}-1H-benzimidazole-6-carbonitrile (6.0 g, 21.33 mmol) followed by N-methyl-2-pyrrolidone (NMP) (20.00 mL). The mixture was heated at 75° C. for 2 days and then cooled to RT. The reaction mixture was diluted with EtOAc/H2O and extracted with 3×EtOAc. The organic layers were washed with 2× brine, dried over Na2SO4, filtered and concentrated. To the residue was added 250 mL of i-PrOH, heated to reflux for 2 hours, and then cooled to RT for 2 days. The solid was filtered and air dried to afford 1-(((5S,7S)-3-(6-methoxypyridin-3-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile as a white solid (7.43 g, 79% yield).

1. temperatureThe mixture was heated at 75° C. for 2 days
2. temperaturecooled to RT
3. extractionextracted with 3×EtOAc
4. washThe organic layers were washed with 2× brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. additionTo the residue was added 250 mL of i-PrOH
9. temperatureheated
10. temperatureto reflux for 2 hours
11. temperaturecooled to RT for 2 days
12. filtrationThe solid was filtered
13. customair dried