Sarcosine → HCID 178446172, compound

Participants

Reaction Steps

4-Hydroxy-3-(7-iodo-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-1-(3-methyl-butyl)-pyrrolo[1,2-b]pyridazin-2-one (Example 6a, 0.188 g, 0.357 mmol), potassium triphosphate (0.379 g, 1.78 mmol), sarcosine (0.019 g, 0.214 mmol), and copper (I) iodide (0.017 g, 0.089 mmol) were combined. Anhydrous N,N-dimethylformamide (7 mL) was added followed by N-methyl-methanesulfonamide (0.39 g, 3.57 mmol). The solution was degassed while stirring under vacuum and the flask purged with nitrogen. The mixture was stirred at 100° C. for 1 h. Additional copper (I) iodide (0.1 g, 0.525 mmol) was added. The mixture continued to stir at 100° C. for 3 h. Upon cooling, the mixture was diluted with ethyl acetate (200 mL), washed with 1.0 M aqueous hydrochloric acid solution (2×100 mL), dried over magnesium sulfate, filtered and concentrated in vacuo to a solid. Purification by flash column chromatography (5% ethyl acetate in dichloromethane) followed by trituration from ethyl acetate and collection by vacuum filtration afforded the desired product, N-{3-[4-hydroxy-1-(3-methyl-butyl)-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}-N-methyl-methanesulfonamide (0.057 g, 0.112 mmol, 31% yield) as a pale yellow powder. 1H NMR (400 MHz, DMSO-d6) δ: 0.97 (6H, d, J=6.4 Hz), 1.59 (2H, q, J=7.6 Hz), 1.73 (1H, septet, J=6.5 Hz), 3.01 (3H, s), 3.31 (3H, s), 4.41 (2H, t, J=7.9 Hz), 6.70-6.72 (1H, m), 7.04 (1H, d, J=4.5 Hz), 7.69-7.76 (2H, m), 7.88 (1H, d, J=2.3 Hz), 7.91 (1H, s), 13.79 (1H, bs). LC-MS (ESI) calcd for C21H25N5O6S2, found 507.12, found 508.4 [M+H+].

Provenance & Evidence