Sarcosine → HCID 178446177, 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 13a, 0.105 g, 0.199 mmol), potassium triphosphate (0.127 g, 0.598 mmol), sarcosine (0.011 g, 0.119 mmol), and copper (I) iodide (0.015 g, 0.080 mmol) were combined. Anhydrous N,N-dimethylformamide (7 mL) was added followed by cyclopropanesulfonic acid amide (0.12 g, 1 mmol). The solution was degassed while stirring under vacuum and the flask purged with nitrogen. The mixture was stirred at 100° C. for 16 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 HPLC (Column Luna 5u C18 (2) 100 Å size 50×21.2 mm, 5 micron, 40%-95% 0.05% trifluoroacetic acid in acetonitrile/0.05% trifluoroacetic acid in water) afforded the desired product, cyclopropanesulfonic acid {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}-amide (0.052 g, 0.10 mmol, 50% yield) as a pale yellow powder. 1H NMR (400 MHz, DMSO-d6) δ: 0.97 (10H, m), 1.51 (2H, q, J=7.2 Hz), 1.73 (1H, m), 2.71 (1H, m), 4.41 (2H, t, J=7.6 Hz), 6.72 (1H, m), 7.02 (1H, d, J=3.6 Hz), 7.58 (1H, m), 7.63 (2H, m), 7.88 (1H, s), 10.12 (1H, bs). LC-MS (ESI) calcd for C22H25N5O6S2. found 519.12. found 520.3 [M+H+].

Provenance & Evidence