反应详情

To a stirred slurry of 4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzoic acid (0.38 g) in DMF (50 ml) was added 4-amino-5-methylisoxazole hydrochloride (0.27 g), HATU (0.68 g) and triethylamine (0.55 ml) and the reaction mixture stirred at room temperature for 16 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The ethyl acetate layer was washed with 1N NaOH and dried (magnesium sulphate). The residue was purified by column chromatography on a silica column using initially ethyl acetate and then a 4:1 mixture of ethyl acetate and methanol as eluent. There was thus obtained the title compound (150 mg); NMR Spectrum: (DMSOd6) 2.15 (s, 3H), 2.40 (s, 3H), 2.83 (m, 4H), 3.15 (s, 3H), 3.40 (m, 4H), 7.50 (d, 1H), 7.60 (d, 1H), 7.64 (m, 2H), 7.98 (s, 1H), 8.04 (d, 1H), 8.13 (s, 1H), 8.70 (s, 1H), 10.10 (s, 1H); Mass Spectrum: M+H+ 459.

1. extractionextracted with ethyl acetate
2. washThe ethyl acetate layer was washed with 1N NaOH
3. dry with materialdried (magnesium sulphate)
4. customThe residue was purified by column chromatography on a silica column
5. additiona 4:1 mixture of ethyl acetate and methanol as eluent