反应详情

温度

0 °C

To a solution of 3-methyl-3-((R)-1-methyl-2-oxo-1,2,3,5-tetrahydro-6-oxa-3,4,10,11b-tetraaza-cyclopenta[b]phenanthren-10-yl)-azetidine-1-carboxylic acid tert-butyl ester (Example #148, Step J, 1 g, 2.35 mmol) in THF (20 mL) was added 1-iodopyrrolidine-2,5-dione (0.582 g, 2.59 mmol) in portions at −5-0° C. The reaction mixture was stirred at 0° C. for 3 h. Saturated aqueous sodium sulphite solution (5 mL) was added to quench the reaction and the solvent was removed in vacuo. The residue was purified by column chromatography on silica gel (eluting with 10%˜100% EtOAc in petroleum ether) to give 3-((R)-8-iodo-1-methyl-2-oxo-1,2,3,5-tetrahydro-6-oxa-3,4,10,11b-tetraaza-cyclopenta[b]phenanthren-10-yl)-3-methyl-azetidine-1-carboxylic acid tert-butyl ester (0.4 g, 30%) as a yellow solid. 1H NMR (400 MHz, methanol-d4): δ 7.39 (s, 1H), 6.97 (s, 1H), 6.89 (s, 1H), 4.97 (m, 1H), 4.53 (d, J=8.5 Hz, 2H), 4.59 (m, 2H), 4.54 (m, 2H), 4.29 (m, 2H), 1.81 (s, 3H), 1.51-1.48 (m, 12H). LC/MS (Table 1, Method 2) Rt=1.279 min.; MS m/z: 552 [M+H]+.

1. customto quench
2. customthe reaction
3. customthe solvent was removed in vacuo
4. customThe residue was purified by column chromatography on silica gel (eluting with 10%˜100% EtOAc in petroleum ether)