反应详情

A mixture of 1-acetylamino-3-azabicyclo[3.1.0]hexane (60 mg, 0.28 mmol) and triethylamine (195 μl, 1.4 mmol) in acetonitrile (10 ml) was treated with the ethyl ester of 7-chloro-6-fluoro-1-(2,4-difluoro-phenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid (95.6 mg, 0.25 mmol) and heated to 80° for 20 hours. The reaction mixture was concentrated in vacuo, diluted with chloroform and washed with saturated aqueous sodium bicarbonate. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was chromatographed on silica gel (eluant: 189:10:1 chloroform:methanol:conc. ammonium hydroxide) to yield the title product as a yellow oil (120.8 mg, 0.25 mmol, 100% yield). 1H NMR (CDCl3) 8.35 (s, 1H), 8.01 (d, J=13 Hz, 1H), 7.36 (m, 1H), 7.04 (m, 2H), 6.11 (bs, 1H), 4.35 (q, J=7 Hz, 2H), 3.96 (vbs, 1H), 3.69 (vbs, 3H), 1.96 (s, 3H), 1.73 (m, 1H), 1.37 (t, J=7 Hz, 3H), 1.06 (m, 1H), 0.71 (m, 1H).

1. temperatureheated to 80° for 20 hours
2. concentrationThe reaction mixture was concentrated in vacuo
3. additiondiluted with chloroform
4. washwashed with saturated aqueous sodium bicarbonate
5. dry with materialThe organic layer was dried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was chromatographed on silica gel (eluant: 189:10:1 chloroform:methanol:conc. ammonium hydroxide)