反应详情

温度

0 °C

4-n-butoxy-3,5-dimethoxybenzoic acid represented by Formula 90 (6 g, 23.60 mmol) prepared in Preparative Example 2 above was slowly added to a solution of 4-(aminomethyl)-N,N-dimethyltetrahydro-2H-pyran-4-amine represented by Formula 95 (3.73 g, 23.60 mmol) and diisopropylethylamine (12.36 mL, 70.78 mmol) in DMF (80 mL) at room temperature. After cooling the reaction mixture to 0° C. and adding 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate methanaminium (HATU, 8.97 g, 23.60 mmol) thereto, the mixture was agitated at room temperature for 24 hours. The reaction solvent was removed under reduced pressure and ethyl acetate was added to the remaining concentrate to prepare a solution. The prepared solution was washed with a potassium carbonate solution, followed by separation to form an organic layer. Then, after drying the organic layer with magnesium sulfate (MgSO4), the solvent was removed again under reduced pressure. The obtained vacuum-concentrated mixture was subjected to separation and purification through column chromatography (chloroform/methanol, 10:1) using silica gel (SiO2). After dissolving the obtained organic product in ethyl acetate, 2 M-ethylether chloride solution (14.16 mL, 28.31 mmol) was added thereto, followed by agitation at 45° C. for 15 minutes. Thereafter, the solvent was filtered to obtain a product in a powder form and the product was recrystallized in ethanol-methanol to thus produce a benzamide compound represented by Formula 6 as a desired product (VVZ-005; 6.77 g, 66% yield).

1. customprepared in Preparative Example 2
2. customThe reaction solvent was removed under reduced pressure and ethyl acetate
3. additionwas added to the
4. concentrationremaining concentrate
5. customto prepare a solution
6. washThe prepared solution was washed with a potassium carbonate solution
7. customfollowed by separation
8. customto form an organic layer
9. dry with materialThen, after drying the organic layer with magnesium sulfate (MgSO4)
10. customthe solvent was removed again under reduced pressure
11. concentrationThe obtained vacuum-concentrated mixture
12. customwas subjected to separation and purification through column chromatography (chloroform/methanol, 10:1)
13. dissolutionAfter dissolving the obtained organic product in ethyl acetate
14. waitfollowed by agitation at 45° C. for 15 minutes
15. filtrationThereafter, the solvent was filtered
16. customto obtain a product in a powder form
17. customthe product was recrystallized in ethanol-methanol