反应详情

1-(3,3-Dimethyl-butyl)-4-hydroxy-3-(7-iodo-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-pyrrolo[1,2-b]pyridazin-2-one (Example 4d, 0.065 g, 0.120 mmol), potassium triphosphate (0.128 g, 0.60 mmol), sarcosine (0.006 g, 0.072 mmol), and copper (I) iodide (0.006 g, 0.03 mmol) were combined. Anhydrous N,N-dimethylformamide (2 mL) was added followed by methanesulfonamide (0.114 g, 1.2 mmol). The solution was degassed while stirring under vacuum and the flask was purged with nitrogen. The mixture was stirred at 100° C. for 2 h. Upon cooling, the mixture was diluted with ethyl acetate (100 mL), washed with 1.0 M aqueous hydrochloric acid solution (3×50 mL) and dried over magnesium sulfate. The entire organic layer was passed through a plug of silica gel. The filtrate was concentrated in vacuo to afford a solid. The solid was triturated with a 1:1 mixture of ethyl acetate and hexanes, collected by vacuum filtration, triturated with methanol and collected by vacuum filtration. The solid was dried in vacuo for 16 h to afford the desired product, N-{3-[1-(3,3-dimethyl-butyl)-4-hydroxy-2-oxo-1,2-dihydro-pyrrolo[1,2-b]pyridazin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide (0.031 g, 0.061 mmol, 51% yield) as a pale yellow powder. 1H NMR (400 MHz, DMSO-d6) δ: 1.01 (9H, s), 1.57-1.62 (2H, m), 3.07 (3H, s), 4.39-4.43 (2H, m), 6.70-6.72 (1H, m), 7.03 (1H, d, J=3.8 Hz), 7.53 (1H, dd, J1=8.7 Hz, J2=2.8 Hz), 7.60 (1H, d, J=2.3 Hz), 7.67 (1H, d, J=8.4 Hz), 7.75 (1H, s), 10.20 (1H, s), 13.72 (1H, bs). LC-MS (ESI) calcd for C21H25N5O6S2, found 507.12, found 508.36 [M+H+].

1. customThe solution was degassed
2. customthe flask was purged with nitrogen
3. stirringThe mixture was stirred at 100° C. for 2 h
4. temperatureUpon cooling
5. additionthe mixture was diluted with ethyl acetate (100 mL)
6. washwashed with 1.0 M aqueous hydrochloric acid solution (3×50 mL)
7. dry with materialdried over magnesium sulfate
8. concentrationThe filtrate was concentrated in vacuo
9. customto afford a solid
10. customThe solid was triturated with a 1:1 mixture of ethyl acetate and hexanes
11. filtrationcollected by vacuum filtration
12. customtriturated with methanol
13. filtrationcollected by vacuum filtration
14. customThe solid was dried in vacuo for 16 h