Hydrochloric Acid → Methyl 5-[(5-bromo-3-formylpyridin-2-yl)(propyl)amino]pentanoate

Temperature

115 °C

To N-propyl-2-piperidone (1.92 g) was added a 4 N aqueous sodium hydroxide solution (6.8 ml), and the mixture was refluxed at 115° C. for 5 hours. Thereto was added concentrated hydrochloric acid (2.27 ml) at 0° C. to neutralize the resulting mixture. Then, sodium carbonate (2.88 g), water (11.5 ml) and DMSO (18.2 ml) were added thereto. After the mixture was heated to 90° C., a solution of 5-bromo-2-chloronicotinaldehyde (1.5 g) in DMSO (23 ml) was added dropwise thereto and the mixture was stirred as it is for 2 hours. After cooling to 0° C., water was added thereto. 6 N Hydrochloric acid (9 ml) was then added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure and the residue as it is was dissolved in DMF (50 ml), and then potassium carbonate (2.31 g) and iodomethane (1.04 ml) were added thereto. The mixture was stirred at room temperature under a nitrogen atmosphere for 2 hours. Water was added thereto and the mixture was then extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:1→hexane:ethyl acetate=4:1) to give methyl 5-[(5-bromo-3-formylpyridin-2-yl)(propyl)amino]pentanoate (909 mg) as a yellow oily material.

1. temperatureAfter the mixture was heated to 90° C.
2. temperatureAfter cooling to 0° C.
3. extractionthe mixture was extracted with ethyl acetate
4. washThe organic layer was washed with saturated brine
5. dry with materialdried over magnesium sulfate
6. distillationThe solvent was distilled off under reduced pressure
7. dissolutionthe residue as it is was dissolved in DMF (50 ml)
8. additionpotassium carbonate (2.31 g) and iodomethane (1.04 ml) were added
9. stirringThe mixture was stirred at room temperature under a nitrogen atmosphere for 2 hours
10. additionWater was added
11. extractionthe mixture was then extracted with ethyl acetate
12. washThe organic layer was washed with saturated brine
13. dry with materialdried over magnesium sulfate
14. distillationThe solvent was distilled off under reduced pressure
15. customthe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:1→hexane:ethyl acetate=4:1)

ORD record

ord-29e1d8a61b564a2084bbb021851a5ac4

Source dataset

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07288654B2