Acetic Acid → HCID 86758522, compound

Temperature

50 °C

To a mixture of 4-[{N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl}aminomethyl]piperidine (0.050 mmol), 5-bromo-2-ethoxybenzaldehyde (0.15 mmol), methanol (1.2 mL), and acetic acid (0.030 mL) was added NaBH3CN (0.25 mmol) in methanol (0.50 mL). The reaction mixture was stirred at 50° C. for 13 h. The mixture was cooled to room temperature, loaded onto Varian™ SCX column, and washed with CH3OH (5 mL×3). Product was eluted off using 2 N NH3 in CH3OH (5 mL) and concentrated. To the resulting material were added dichloromethane (1 mL) and trifluoroacetic acid (TFA) (0.50 mL) and the solution was stirred at room temperature for 10 min. The reaction mixture was concentrated, and 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 (SiO2, ethyl acetate/methanol=10/1) gave 4-[{N-(2-amino-4,5-difluorobenzoyl)glycyl)amino}methyl]-1-(5-bromo-2-ethoxybenzyl)piperidine (Compound No. 2052) (10.2 mg, 38%): The purity was determined by RPLC/MS (96%); ESI/MS m/e 539.2 (M++H, C24H29BrF2N4O3).

1. temperatureThe mixture was cooled to room temperature
2. washwashed with CH3OH (5 mL×3)
3. washProduct was eluted off
4. concentrationconcentrated
5. additionTo the resulting material were added dichloromethane (1 mL) and trifluoroacetic acid (TFA) (0.50 mL)
6. stirringthe solution was stirred at room temperature for 10 min
7. concentrationThe reaction mixture was concentrated
8. dissolutionthe residue was dissolved in methanol
9. washwashed with CH3OH (5 mL×2)
10. washProduct was eluted off
11. concentrationconcentrated

ORD record

ord-8f84f77ea8f9456499d064535667ccb1

Source dataset

uspto-grants-2002_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06451842B1