Acetic Acid → 4-[[N-(2-amino-4,5-difluorobenzoyl)glycyl]aminomethyl]-1-(2-hydroxy-3-methylbenzyl)piperidine

温度

50 °C

To a mixture of 4-[{N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl}aminomethyl]piperidine (0.050 mmol), 2-hydroxy-3-methylbenzaldehyde (0.25 mmol), methanol (1.0 mL), and acetic acid (0.040 mL) was added NaBH3CN (0.40 mmol) in methanol (0.50 mL). The reaction mixture was stirred at 50° C. overnight. The mixture was cooled to room temperature, loaded onto Varian™ SCX column, and washed with CH3OH (5 mL×2). Product was eluted off using 2 N NH3 in CH3OH (5 mL) and concentrated. The resulting material was dissolved into ethyl acetate/methanol=5:1 (1 mL), loaded onto Varian™ Si column, eluted off using ethyl acetate/methanol=5:1 (5 mL), and concentrated. The residue was dissolved in methanol (2 mL) and 4 N HCl in dioxane (0.50 mL) was added. The solution was stirred at room temperature overnight and concentrated. The residue was dissolved in methanol, loaded onto Varian™ SCX column, and washed with CH3OH (5 mL×2). Product was eluted off using 2 N NH3 in CH3OH (5 mL) and concentrated. Preparative TLC afforded 4-[{N-(2-amino-4,5-difluorobenzoyl)glycyl}aminomethyl]-1-(2-hydroxy-3-methylbenzyl)piperidine (Compound No. 2106): The purity was determined by RPLC/MS (97%); ESI/MS m/e 447.0 (M++H, C23H28F2N4O3).

1. temperatureThe mixture was cooled to room temperature
2. washwashed with CH3OH (5 mL×2)
3. washProduct was eluted off
4. concentrationconcentrated
5. dissolutionThe resulting material was dissolved into ethyl acetate/methanol=5:1 (1 mL)
6. washeluted off
7. concentrationconcentrated
8. dissolutionThe residue was dissolved in methanol (2 mL)
9. addition4 N HCl in dioxane (0.50 mL) was added
10. stirringThe solution was stirred at room temperature overnight
11. concentrationconcentrated
12. dissolutionThe residue was dissolved in methanol
13. washwashed with CH3OH (5 mL×2)
14. washProduct was eluted off
15. concentrationconcentrated

ORDレコード

ord-38dd18c5656d49bcad999aa7612e8b0e

出典データセット

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06362177B1