Example 2: Synthesis of 2-{4-[2-(3,5-dimethyl-pyrazol-1-yl)-acetyl]-piperazin-1-yl}-N-pyridin-4-yl-benzamide
1. 2-(Piperazin-1-yl)benzoic acid (1.000 g, 4.89 mmol) was suspended in 10 mL of methanol.
2. 5 mL of concentrated sulfuric acid was slowly added to the suspension.
3. The reaction mixture was stirred for 16 h. A white precipitate was observed.
4. 5 mL of concentrated sulfuric acid and 10 mL of methanol were added.
5. The reaction volume was expanded by adding 200 mL of methanol and 60 mL of concentrated sulfuric acid and the mixture was continued to be stirred for 2 hours.
6. Heat the reaction mixture to reflux and maintain for 12 hours.
7. Concentrate the reaction volume to about 175mL.
8. The concentrated mixture was upsampled to an ion exchange column and eluted with 5 x 200mL of 10% ammonia/methanol solution.
9. The product eluate was collected and concentrated.
10. The concentrate was co-evaporated with toluene to remove residual water to give 0.667 g of methyl 2-piperazin-1-yl-benzoate in 63% yield.
