Dichloromethane → HCID 67209538, compound

To the solution of 2-methyl-6,7-dihydro-5H-cyclopenta[b]pyridin-5-one ([173064-91-0], 0.275 g, 1.87 mmol) in MeOH (15 ml) was added ammonium acetate (7.2 g, 93 mmol) and the mixture was stirred at rt of 30 min. Sodium cyanoborohydride (0.176 g, 2.80 mmol) was added in portions and the reaction was heated at reflux temperature over night. Most of the solvent was evaporated under reduced pressure and the residue taken in to into EtOAc and 2N aqueous sodium hydroxide. The aqueous layer was separated and dioxane (50 ml) was added, followed by di-tert-butyl dicarbonate (2.04 g, 9.34 mmol). The mixture was stirred at rt for 3 h. The organic layer was separated and most of the solvent evaporated under reduced pressure and the residue was taken in EtOAc. The solution was washed with brine, dried over sodium sulfate and the solvent was evaporated under reduced pressure. The intermediate was purified by chromatography on silica (Flashmaster, hex/EtOAc 1/1 to EtOAc over 15 min, EtOAc to EtOAc/MeOH 9/1 over 15 min). The obtained colorless solid was dissolved in 4 N HCl in dioxane and the reaction was stirred at rt for 2 h. The residue obtained by evaporation of the solvent was redissolved in DCM and the solvent was evaporated again to give the title compound as white solid. [1H-NMR (DMSO-d6, 600 MHz) δ 8.71 (br s, 3H), 8.32 (br s, 1H), 7.54 (br s, 1H), 4.82 (br s, 1H), 3.33-3.25 (m, 1H), 3.12-3.05 (m, 1H), 2.64 (s, 3H), 2.62.2.52 (m, 1H), 2.16-2.11 (m, 1H); MS [M+H]+=149.0]

1. temperaturethe reaction was heated
2. temperatureat reflux temperature over night
3. customMost of the solvent was evaporated under reduced pressure
4. customThe aqueous layer was separated
5. additiondioxane (50 ml) was added
6. stirringThe mixture was stirred at rt for 3 h
7. customThe organic layer was separated and most of the solvent
8. customevaporated under reduced pressure
9. washThe solution was washed with brine
10. dry with materialdried over sodium sulfate
11. customthe solvent was evaporated under reduced pressure
12. customThe intermediate was purified by chromatography on silica (Flashmaster, hex/EtOAc 1/1 to EtOAc over 15 min, EtOAc to EtOAc/MeOH 9/1 over 15 min)
13. dissolutionThe obtained colorless solid was dissolved in 4 N HCl in dioxane
14. stirringthe reaction was stirred at rt for 2 h
15. customThe residue obtained by evaporation of the solvent
16. customthe solvent was evaporated again

ORD record

ord-24a440620c82408b87f2f96d763f1999

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08742106B2