Hydrochloric Acid → (2-(4-Chlorophenyl)-4-methyloxazol-5-yl)(2-((pyridin-3-yloxy)methyl)piperazin-1-yl)methanone trihydrochloride

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Reaction Steps

TBTU (141 mg, 0.438 mmol) was added to a solution of Intermediate C (86 mg, 0.29 mmol), 2-(4-chlorophenyl)-4-methyloxazole-5-carboxylic acid (76 mg, 0.32 mmol), and triethylamine (0.123 mL, 0.876 mmol) in DMF (4 mL). After stirring overnight, 1N NaOH (3 mL) was added, and the reaction mixture was stirred for 30 min. Water (15 mL) was added, and the reaction mixture was extracted with EtOAc (3×40 mL). The EtOAc extracts were combined, washed with aqueous NaOH (2×10 mL) and brine (10 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The material was purified by HPLC (5 to 95% MeCN/0.1% TFA in H2O/0.1% TFA gradient), yielding a yellow oil. The material was dissolved in MeOH (1 mL) and treated with 4 M HCl in 1,4-dioxane (5 mL, 20 mmol). After stirring for 5 h, the reaction mixture was concentrated under reduced pressure and purified by HPLC (5 to 95% MeCN/0.1% TFA in H2O/0.1% TFA gradient) to give 37.2 mg (24%) of the title compound as a white solid. LC-MS: RT=4.74 min, [M+H]+=413.6.

Provenance & Evidence