Sarcosine → HCID 178482063, compound

Participants

Reaction Conditions

Reaction Steps

1-(4-Fluoro-benzyl)-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 9b, 0.269 g, 0.477 mmol), potassium phosphate (tribasic) (0.506 g, 2.38 mmol), copper (I) iodide (0.023 g, 0.119 mmol), sarcosine (0.026 g, 0.290 mmol, and N-methyl-methanesulfonamide (0.520 g, 4.77 mmol) were dissolved in N,N-dimethylformamide (9 mL) at 25° C. The mixture was heated to 100° C. for 6 h, then was allowed to cool to 25° C., diluted with ethyl acetate (10 mL), and filtered through Celite. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography (Merck silica gel 60, 40-63 μm, 0→10% methanol in dichloromethane) to afford a yellow solid. Sequential trituration of this material with methanol and diethyl ether afforded the desired product, N-{3-[1-(4-fluoro-benzyl)-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}-N-methyl-methanesulfonamide (0.169 g, 0.31 mmol, 65% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ: 3.02 (3H, s), 3.31 (3H, s), 5.65 (2H, s), 6.59-6.61 (1H, m), 7.01-7.03 (1H, m), 7.14-7.19 (2H, m), 7.42-7.46 (2H, m), 7.68-7.71 (2H, m), 7.75 (1H, dd, J1=2.4 Hz, J2=8.7 Hz), 7.90 (1H, d, J=2.2 Hz), 13.72 (1H, s). LC-MS (ESI) calcd for C23H20FN5O6S2 545.08. found 546.15 [M+H+].

Provenance & Evidence