184177-81-9

170985-85-0

184177-83-1

Synthesis of 4-(4-(4-(4-(4-hydroxyphenyl)-1 -piperidinyl)phenyl)-2-[(1S,2S)-1 -ethyl-2-(benzyloxy)propyl]-2,4-dihydro-3H-1 ,2,. 4-triazol-3-one was carried out in the following general steps: the N'-((2S,3S)-2-(benzyloxy)pentan-3-yl)formylhydrazine compound of formula-17 obtained in Example 13 (45.5 g) was mixed with dioxane (500 ml), and 4-(4-(4-hydroxyphenyl)piperazin-1-yl)phenylcarbamate compound (50 g) was added and heated to 90-100 °C. Triethylamine (26 g) was added to the reaction mixture at 90-100 °C and kept at this temperature with stirring for 24 hours. After completion of the reaction, the reaction mixture was cooled to 25-30 °C and dichloromethane was added. The reaction mixture was filtered through a hyflow bed and washed with dichloromethane. Water was added to the filtrate to separate the organic and aqueous layers, and the aqueous layer was extracted with dichloromethane. The organic layers were combined and washed sequentially with 2% sodium hydroxide solution, water, 5% hydrochloric acid solution, water, and 5% NaHCO3 solution. The solvent in the organic layer was distilled under reduced pressure to obtain the target product. Isopropanol (75 ml) was added to the resulting compound, cooled to 25-30°C and stirred for 6 hours. The solid was filtered, washed with isopropanol and dried to give 4-(4-(4-(4-hydroxyphenyl)-1-piperidinyl)phenyl)-2-[(1S,2S)-1-ethyl-2-(phenylmethoxy)propyl]-2,4-dihydro-3H-1,2,4-triazol-3-one. Yield: 28 g; HPLC purity: 97.67%; impurity-A: 0.37%. b) Purification of compound of formula-20: The obtained compound of formula-20 (30 g) was dissolved in methanol (960 ml) and heated to 60-65°C to dissolve. The reaction mixture was cooled to 25-30°C and stirred at the same temperature for 30 min. The precipitated solid was filtered and dried to give pure compound of formula-20. Yield: 70%; HPLC purity: 99.15%; impurity-A: 0.09%.