反应详情

温度

82.5 °C

To a mixture of 4-Chloro-5,8-dihydro-6H-9-thia-1,3,7-triaza-fluorene-7-carboxylic acid tert-butyl ester (6.86 g, 0.021 mol) and 3-chloro-4-fluoroaniline (3.2 g, 0.022 mol) in 2-propanol (96 ml) was added 4 N HCl in Dioxane (0.27 ml) and the mixture heated to 80-85° C. overnight. LCMS and TLC (5% MeOH/DCM) indicate that no SM (Boc-protected SM) present. 4 N HCl in Dioxane (10.5 ml, 0.042 mol) added and the heating continued until LCMS indicates no Boc-protected product present. Cooled to RT and conc. to dryness. The mixture was then suspended in dichloromethane (200 ml) and stirred with 1N NaOH (200 ml) for 30 min. Clear biphasic layers obtained. Layers separated and the aqueous washed with dichloromethane (100 ml). Combined organic layers washed with water (2×100 ml), then with brine (100 ml). Dried the organic layer with sodium sulfate, filtered and conc. to dryness. Dried under vacuum at to give 6.61 g (94%) of the product as indicated by LCMS and HNMR. 1H NMR (DMSO-d6) δ 8.41 (s, 1H), 8.24 (s, 1H), 7.92 (m, 1H), 7.64 (m, 1H), 7.39 (t, J=9.4 Hz, 1H), 3.94 (broad s, 1H), 3.32 (m, 2H), 3.05 (m, 2H), 3.01 (m, 2H); LCMS RT=2.13 min, [M+H]+=335.

1. temperatureCooled to RT and conc. to dryness
2. customobtained
3. customLayers separated
4. washthe aqueous washed with dichloromethane (100 ml)
5. washCombined organic layers washed with water (2×100 ml)
6. dry with materialDried the organic layer with sodium sulfate
7. filtrationfiltered and conc. to dryness
8. customDried under vacuum at