1,2-Dichloroethane → 3'-(4-Fluoro-phenyl)-4-(1-phenyl-1h-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2h-[1,2']bipyrazine hydrochloride salt

関与物質

反応手順

Form the free base of 3′-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl dihydrochloride by SCX-2® chromatography washing with methanol then eluting with 2M ammonia in methanol. Dissolve 3′-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.200 g, 0.774 mmol) in DCE (5 mL). Add 1-phenyl-1H-pyrazole-4-carbaldehyde (0.200 g, 1.16 mmol, 1.5 eq.). Stir at room temperature for 20-30 min. Add sodium triacetoxyborohydride (0.33 g, 1.55 mmol, 2 eq.) followed by acetic acid (0.048 g, 0.81 mmol, 1.05 eq.). Stir the reaction mixture at room temperature for 48 hr. Purify by SCX cartridge, followed by reverse phase chromatography to obtain the freebase of the title compound (0.360 g, 0.87 mmol, 100% yield). MS (ES): m/z=415.3[M+H]. Dissolve in methanol (5 mL). Add ammonium chloride (0.047 g, 0.87 mmol, 1 eq.). Stir the reaction mixture at room temperature for 2 hr. and concentrate to give the title compound (0.327 g, 83% yield for salt formation). MS (ES): m/z=415.3[M+H]+.

情報源と証拠