Benzylamine → HCID 9794807, compound

Temperature

120 °C

The 3-chloro-1-(3-pyridyloxy)propane (0.65 g, 3.78 mmol) was dissolved in methanol (20 mL) and added to a mixture of benzylamine (13.5 mL) in water (20 mL) in a heavy-walled glass pressure-tube apparatus. The tube was sealed and the mixture was stirred and heated at 120° C. (oil bath temperature) for 3 h. After cooling, the mixture was concentrated by rotary evaporation, and saturated NaCl solution (25 mL) was added to the residue. The mixture was acidified to pH 1 with 10% HCl solution and extracted with CHCl3 (2×35 mL) to remove impurities. The aqueous phase was basified to pH 10 with 10% NaOH solution, and the mixture was extracted with chloroform (4×50 mL). The combined chloroform extracts were dried (MgSO4), filtered, and concentrated by rotary evaporation to a residue that was dried briefly under high vacuum to give a brown oil. The oil was concentrated by vacuum distillation to remove excess benzylamine (bp 85° C. at 15 mm Hg). The remaining residue (0.483 g) was purified by column chromatography on silica gel (25 g) eluting with CH3OH—NH4OH (50:1, v/v). Fractions containing the product (Rf 0.39) were combined and concentrated on a rotary evaporator. The residue was re-chromatographed on silica gel (10 g). Fractions containing the product were combined and concentrated on a rotary evaporator. The residue was dissolved in CHCl3 and the CHCl3 solution was dried (MgSO4), filtered, and concentrated by rotary evaporation to a residue that was dried briefly under high vacuum to give 20 mg (2.2%) of a light-brown oil. The compound exhibits a Ki of 3000 nM. The compound exhibits neurotransmitter release of 29 percent.

1. customThe tube was sealed
2. temperatureAfter cooling
3. concentrationthe mixture was concentrated by rotary evaporation, and saturated NaCl solution (25 mL)
4. additionwas added to the residue
5. extractionextracted with CHCl3 (2×35 mL)
6. customto remove impurities
7. extractionthe mixture was extracted with chloroform (4×50 mL)
8. dry with materialThe combined chloroform extracts were dried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated by rotary evaporation to a residue that
11. customwas dried briefly under high vacuum
12. customto give a brown oil
13. concentrationThe oil was concentrated by vacuum distillation
14. customto remove excess benzylamine (bp 85° C. at 15 mm Hg)
15. customThe remaining residue (0.483 g) was purified by column chromatography on silica gel (25 g)
16. washeluting with CH3OH—NH4OH (50:1
17. additionFractions containing the product (Rf 0.39)
18. concentrationconcentrated on a rotary evaporator
19. customThe residue was re-chromatographed on silica gel (10 g)
20. additionFractions containing the product
21. concentrationconcentrated on a rotary evaporator
22. dissolutionThe residue was dissolved in CHCl3
23. dry with materialthe CHCl3 solution was dried (MgSO4)
24. filtrationfiltered
25. concentrationconcentrated by rotary evaporation to a residue that
26. customwas dried briefly under high vacuum

ORD record

ord-555ffcaf1360417a897c40fa1a54ece5

Source dataset

uspto-grants-2003_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06627648B1