反应详情

To a suspension of 2-{3-[4-(6-Methoxy-[1,5]naphthyridin-4-yl)-[1,2,3]triazol-1-yl]-propyl)-isoindole-1,3-dione (180 mg, 0.43 mmole) in ethanol (3 mL) was added hydrazine hydrate (23 μL, 0.48 mmole) and the mixture was brought to reflux for 3 hours. After cooling 0.1 mL of 6N aqueous HCl was added to dissolve the product. The mixture was filtered and the filtrate was concentrated to dryness to afford the crude amine hydrochloride (85 mg). This material was suspended in chloroform (3 mL) and treated with triethylamine (0.18 mL, 1.3 mmole), followed by 3-oxo-3,4-dihydro-2H benzo[1,4]thiazine-6-sulfonyl chloride (100 mg, 0.4 mmole). After stirring 1 hour the mixture was diluted with chloroform, washed with saturated aqueous NaHCO3, dried (MgSO4), and chromatographed on silica (0–5% methanovchloroform) to provide the title compound as an off-white solid (60 mg, 27%). 1H NMR (400 MHz, DMSO-d6): 10.83 (br s, 1 H); 9.05 (s, 1 H); 8.84 (d, 1H); 8.37 (d, 1H); 8.29 (d, 1H); 7.85 (m, 1H); 7.46 (d, 1H); 7.24–7.42 (m, 3H); 4.60 (m, 2H); 4.17 (s, 3H); 3.53 (s, 2H); 2.80 (m, 2H); 2.14 (m, 2H). LC-MS (ES) m/e 512 (M+H)+.

1. temperatureto reflux for 3 hours
2. additionwas added
3. dissolutionto dissolve the product
4. filtrationThe mixture was filtered
5. concentrationthe filtrate was concentrated to dryness
6. customto afford the crude amine hydrochloride (85 mg)
7. washwashed with saturated aqueous NaHCO3
8. dry with materialdried (MgSO4)
9. customchromatographed on silica (0–5% methanovchloroform)