反应详情

Dissolve 3′-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.150 g, 0.581 mmol) in DCE (5 mL). Add 1-(2,2,2-trifluoro-ethyl)-1H-pyrazole-4-carbaldehyde (0.124 g, 0.697 mmol) followed by sodium triacetoxyborohydride (0.185 g, 0.872 mmol) and stir at ambient temperature for 18 hr. Add 1-(2,2,2-trifluoro-ethyl)-1H-pyrazole-4-carbaldehyde (0.062 g, 0.349 mmol) and stir at ambient temperature for 2 hr. Add sodium triacetoxyborohydride (0.092 g, 0.436 mmol) and stir at ambient temperature for 72 hr. Purify via SCX chromatography. Add resin-bound-isocyanate (0.796 g, 1.16 mmol) and DCM (8 mL) and shake at ambient temperature for 4 hr. Filter, concentrate and purify (silica gel chromatography, eluting with 100:0 to 0:100 hexanes:ethyl acetate, then 10:90 methanol:ethyl acetate) to give the free base of the title compound (103 mg, 42%). Dissolve the free base (0.099 g, 0.237 mmol) in methanol and add a solution of ammonium chloride (0.013 g, 0.237 mmol) in a minimal volume of methanol. Shake for 18 hr. at ambient temperature and concentrate to give the title compound (108 mg, 100%). MS (ES): m/z=421[M+H]+.

1. customPurify via SCX chromatography
2. filtrationFilter
3. concentrationconcentrate
4. custompurify (silica gel chromatography
5. washeluting with 100:0 to 0:100 hexanes