反应详情

温度

50 °C

To a solution of 7-(4-chlorobenzyl)-8-(isopropylsulfonyl)-3-methyl-1H-purine-2,6(3H,7H)-dione (80 mg, 0.20 mmol) in DMF (5 mL) was added 5-(chloromethyl)isoxazole (55 mg, 0.5 mmol, intermediate 41), potassium carbonate (58 mg, 0.42 mmol), and TBAI (2 mg, 0.02 mmol). The reaction was heated at 50° C. overnight. The mixture was cooled and partitioned between ethyl acetate and water. The combined organic layer was dried over sodium sulfate, filtered and concentrated to give a crude product which was purified by preparative HPLC to give 7-(4-chlorobenzyl)-8-(isopropylsulfonyl)-1-(isoxazol-5-ylmethyl)-3-methyl-1H-purine-2,6(3H,7H)-dione (39 mg, 40.6% yield) as a white solid. 1H-NMR (CD3OD) δ 8.49(d, 1H), 7.41(dd, 2 H), 7.28(d, 2H), 6.43(d, 1H), 5.87(s, 2H), 5.21(s, 2H), 3.60-3.73(m, 1H), 3.47(s, 3H), 1.25(d, 6H). LCMS retention time 2.772 min; LCMS MH+ 478

1. temperatureThe mixture was cooled
2. custompartitioned between ethyl acetate and water
3. dry with materialThe combined organic layer was dried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated
6. customto give a crude product which
7. customwas purified by preparative HPLC