반응 #434625
ord-cb595adce3014ef98ebdd70ad2f7280e
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후처리
- 1온도The solution was cooled
- 2세척washed on with water
- 3기타The column was flushed successively with water (200 ml), methanol/water (1:1; 200 ml) and methanol (200 ml)
- 4세척The product was eluted off the column with methanol
- 5workup.ADDITIONcontaining triethylamine (1%)
- 6workup.ADDITIONThe fractions containing the product
- 7기타evaporated
- 8기타The residue was further purified by chromatography on a Redisep silica cartridge (40 g)
- 9세척eluting with a gradient of methanol in dichloromethane (5–20%)
실험 절차
A mixture of 3-cyano-7-fluoro-4-hydroxy-5-(tetrahydro-2H-pyran-4-yloxy)quinoline (864 mg), 3-morpholin-4-ylpropan-1-ol (876 mg) and potassium tert-butoxide (1.0M solution in tetrahydrofuran; 9.0 ml) in anhydrous dimethyl sulphoxide (30 ml) was heated at 60° C. for 8 hours. The solution was cooled and then diluted with water (120 ml). Acetic acid was added until pH5 was reached. The solution was pumped onto a cation exchange cartridge (Waters Oasis MCX 6.0 g) and washed on with water. The column was flushed successively with water (200 ml), methanol/water (1:1; 200 ml) and methanol (200 ml). The product was eluted off the column with methanol containing triethylamine (1%). The fractions containing the product were combined and evaporated. The residue was further purified by chromatography on a Redisep silica cartridge (40 g) eluting with a gradient of methanol in dichloromethane (5–20%). This gave the title compound as an white solid (540 mg, 44%); NMR spectrum: (DMSOd6; 373° K) 1.73 (m, 2H), 1.91 (m, 4H), 2.39 (m, 4H), 2.45 (t, 2H), 3.49 (m, 2H), 3.58 (m, 4H), 3.95 (m, 2H), 4.10 (t, 2H), 4.64 (m, 1H), 6.46 (d, 1H), 6.60 (d, 1H), 8.24 (s, 1H); Mass spectrum: M+H+ 414.