4-Methylmorpholine → HCID 135955714, compound

Participants

Reaction Conditions

Reaction Steps

cis-2-(3,3-Dimethyl-butylamino)-cyclooctanecarboxylic acid methyl ester (0.18 g, 0.67 mmol) was dissolved in anhydrous N,N-dimethylformamide (8 mL). (7-Methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid (prepared as described in Example 1j, 0.23 g, 0.67 mmol) was added followed by N-methylmorpholine (0.15 mL, 1.40 mmol). The mixture was stirred until everything dissolved, approximately 5 min. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.13 g, 0.70 mmol) was added and the mixture was stirred at 25° C. for 4 h. Triethylamine (0.28 mL, 2.00 mmol) was added and the mixture was stirred at 50° C. for 16 h. Upon cooling to 25° C., the solution was diluted with ethyl acetate (50 mL) and washed with 1.0 M aqueous hydrochloric acid solution (2×50 mL), saturated aqueous brine solution (20 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo to afford a golden oil. Purification by flash column chromatography (Teledyne Isco RediSep Flash Column; 0-20% ethyl acetate in dichloromethane) afforded the desired product, N-{3-[1-(3,3-dimethyl-butyl)-4-hydroxy-2-oxo-1,2,4a,5,6,7,8,9,10,10a-decahydro-cycloocta[b]pyridin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide (0.18 g, 0.32 mmol, 48%), as a white powder. 1H NMR (400 MHz, DMSO-d6) δ: 1.02 (9H, s), 1.42-2.21 (14H, m), 2.80-2.86 (1H, m), 3.06 (3H, s), 3.11-3.15 (1H, m), 3.66-3.70 (1H, m), 3.99-4.04 (1H, m), 6.57 (1H, s), 7.22-7.26 (1H, m), 7.60-7.66 (2H, m). LC-MS (ESI) calcd for C25H36N4O6S2 552.71, found 553.3 [M+H+].

Provenance & Evidence