反应详情

NaBH3CN (0.40 mmol) was added to a mixture of 4-[[N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl]aminomethyl]piperidine (0.050 mmol) with 2-hydroxy-3-methylbenzaldehyde (0.25 mmol), methanol (1.0 mL) and acetic acid (0.040 mL). The resulting mixture was stirred at 50 overnight, cooled to room temperature, loaded onto a Varian™ SCX column and washed with methanol (5 mL×2). The obtained crude product was eluted with a 2 M methanol solution of NH3 (5 mL) and concentrated. The residue was dissolved in ethyl acetate/methanol=5:1 (1 mL), loaded onto a Varian™ SCX column, eluted with ethyl acetate/methanol=5:1 (5 mL) and concentrated. The residue was dissolved in methanol (2 mL), and a 4 M dioxane solution of HCl (0.50 mL) was added to the resulting solution. The obtained mixture was stirred at room temperature overnight and concentrated. The residue was dissolved in methanol, loaded onto a Varian™ SCX column and washed with methanol (5 mL×2). The obtained crude product was eluted with a 2 M methanol solution of NH3 (5 mL), concentrated and purified by preparative TLC to thereby provide 4-[[N-(2-amino-4,5-difluorobenzoyl) glycyl]aminomethyl]-1-(2-hydroxy-3-methylbenzyl)piperidine (Compd. No. 2106). The purity was determined by RPLC/MS (97%). ESI/MS m/e 447.0 (M++H, C23H28F2N4O3).

1. washwashed with methanol (5 mL×2)
2. customThe obtained crude product
3. washwas eluted with a 2 M methanol solution of NH3 (5 mL)
4. concentrationconcentrated
5. dissolutionThe residue was dissolved in ethyl acetate/methanol=5:1 (1 mL)
6. washeluted with ethyl acetate/methanol=5:1 (5 mL)
7. concentrationconcentrated
8. dissolutionThe residue was dissolved in methanol (2 mL)
9. additiona 4 M dioxane solution of HCl (0.50 mL) was added to the resulting solution
10. stirringThe obtained mixture was stirred at room temperature overnight
11. concentrationconcentrated
12. dissolutionThe residue was dissolved in methanol
13. washwashed with methanol (5 mL×2)
14. customThe obtained crude product
15. washwas eluted with a 2 M methanol solution of NH3 (5 mL)
16. concentrationconcentrated
17. custompurified by preparative TLC to thereby provide 4-[[N-(2-amino-4,5-difluorobenzoyl) glycyl]aminomethyl]-1-(2-hydroxy-3-methylbenzyl)piperidine (Compd. No