反应详情

温度

0 °C

3-Benzyloxycarbonylamino-cyclohexanecarboxylic acid (0.277 g, 1.0 mmol), TEA (0.10 g, 1.0 mmol), and HOBt (0.135 g, 1.0 mmol) were added sequentially to a stirred solution of 3,4-diamino-1-methyl-1H-[1,8]naphthyridin-2-one (0.19 g, 1.0 mmol) in DMF (8 mL) at room temperature. The solution was cooled to 0° C. and EDCI (0.19 g, 1.0 mmol) was added. The resulting solution was allowed to stir, with warming to room temperature, for 17 h. The mixture was diluted with water (5 mL) and extracted with CH2Cl2, dried with MgSO4, and concentrated. The residue was purified by flash chromatography eluting with 5% MeOH in CH2Cl2 to give [3-(4-amino-1-methyl-2-oxo-1,2-dihydro-[1,8]naphthyridin-3-ylcarbamoyl)-cyclohexyl]-carbamic acid benzyl ester (55 mg, 12% yield), and 60 mg (32%) of unreacted diamine. 1H-NMR (CDCl3): δ 8.59 (m, 1H), 8.21 (m, 1H), 7.91 (m, 1H), 7.33 (m, 6H), 7.20 (dd, 1H, J=8.0, 4.8), 5.51 (m, 2H), 5.12 (m, 2H), 4.76 (m, 1H), 4.10 (m, 1H), 3.81 (s, 3H), 2.60 (m, 1H), 2.33 (m, 1H), 1.93-2.05 (m, 3H), 1.73 (m, 2H), 1.45 (m, 2H). MS: calculated for C24H27N5O4+H 450.2; found: 450.5.

1. temperaturewith warming to room temperature, for 17 h
2. extractionextracted with CH2Cl2
3. dry with materialdried with MgSO4
4. concentrationconcentrated
5. customThe residue was purified by flash chromatography
6. washeluting with 5% MeOH in CH2Cl2