反应详情

温度

100 °C

To a suspension of 1-[2-(2,5-dichloro-phenoxy)-pyridine-3-carbonyl]-2,3-dihydro-1H-quinolin-4-one (50 mg, 0.12 mmol, 1.0 equiv; Example 128) in ethanol (1.2 mL) was added 3,3-difluoroazetidine hydrochloride (31 mg, 0.24 mmol, 2.0 equiv; [CAS RN 288315-03-7]), acetic acid (27 mg, 26 μL, 0.48 mmol, 4.0 equiv; [CAS RN 64-19-7]) and N-ethyldiisopropylamine (31 mg, 42 μL, 0.24 mmol, 2.0 equiv; [CAS RN 7087-68-5]). The reaction mixture was heated by microwave irradiation to 100° C. for 10 min. Sodium triacetoxyborohydride (33 mg, 0.16 mmol, 1.3 equiv; [CAS RN 56553-60-7]) was added and heating at 100° C. continued for 15 min. The reaction mixture was extraction from a sat. solution of NaHCO3 (50 mL) with ethyl acetate (3×50 mL) and the combined organic phases dried over MgSO4. Purification by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane/ethyl acetate afforded 0.04 g (7%) of the title compound as a light yellow solid. MS (ISP): 490.0 [M+H]+.

1. temperatureheating at 100° C.
2. extractionextraction from a sat. solution of NaHCO3 (50 mL) with ethyl acetate (3×50 mL)
3. dry with materialthe combined organic phases dried over MgSO4
4. customPurification by silica column chromatography
5. washeluting with a gradient of heptane/ethyl acetate