反应详情

Sodium hydride (81.8 mg, 2.0 mmol) was added to a solution of cis-3-(benzothiazol-2-ylamino)-cyclobutanol (150 mg, 0.68 mmol) in DMF (3 mL) under argon and the mixture was stirred for 1 h at RT. Then 2,5-difluoro-3-(tetrahydro-pyran-4-yl)-pyridine (162 mg, 0.82 mmol) was added and the mixture was heated to 100° C. for 2 h. It was cooled to RT and EtOAc (25 mL) and saturated NH4Cl (15 mL) were added. The organic layer was separated, washed with water (2×25 mL), brine (25 mL), dried over MgSO4, filtered and concentrated in vacuo to give an oil, which was purified by prep-HPLC to give trans-benzothiazol-2-yl-{3-[5-fluoro-3-(tetrahydro-pyran-4-yl)-pyridin-2-yl]-cyclobutyl}-amine (30 mg, yield 10%). [M+1] 400. IC50 (uM) 0.0001.

1. temperaturethe mixture was heated to 100° C. for 2 h
2. temperatureIt was cooled to RT
3. customThe organic layer was separated
4. washwashed with water (2×25 mL), brine (25 mL)
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customto give an oil, which
9. customwas purified by prep-HPLC