Ethanol → HCID 136132920, compound

Participants

Reaction Conditions

Reaction Steps

2,5-Dimethyl-2-phenylaminomethyl-hexanoic acid ethyl ester (0.10 g, 0.36 mmol) was dissolved in N,N-dimethylformamide (4 mL). [7-(Methanesulfonylamino-methyl)-1,1-dioxo-1,4-dihydro-1λ6-thieno[2,3-e][1,2,4]thiadiazin-3-yl]-acetic acid (prepared as described in Example 2c; 0.127 g, 0.36 mmol) was added followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.083 g, 0.43 mmol). The mixture was stirred at 25° C. for 5 h. The solvent was removed in vacuo then re-dissolved in ethanol. A 21 wt. % solution of sodium ethoxide in ethanol (806 μL, 2.16 mmol) was added to the mixture and stirred at 60° C. for 16 h. Upon cooling to 25° C., the mixture was concentrated in vacuo to afford a thick oil. The oil was partitioned between dichloromethane (4 mL) and 1.0 M aqueous hydrochloric acid solution (6 mL). The organic phase was loaded directly onto a prepacked RediSep silica gel column and purified by flash column chromatography (Teledyne Isco RediSep column; 20-100% ethyl acetate in hexanes) to afford the desired product, N-{3-[4-hydroxy-5-methyl-5-(3-methyl-butyl)-2-oxo-1-phenyl-1,2,5,6-tetrahydro-pyridin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-thieno[2,3-e][1,2,4]thiadiazin-7-ylmethyl}-methanesulfonamide (0.079 g, 0.1401 mmol, 39%), as an off white powder. 1H NMR (400 MHz, Acetone-d6) δ: 0.90 (6H, d, J=8.0 Hz), 1.25-1.38 (2H, m), 1.49-1.59 (1H, m), 1.80-1.89 (2H, m), 2.08 (3H, s), 2.96 (3H, s), 3.78-3.85 (2H, m), 4.44 (2H, d, J=6.1 Hz), 6.42 (1H, t, J=6.3 Hz), 7.31-7.48 (6H, m). LC-MS (ESI) calculated for C24H30N4O6S3 566.13. found 567.2 [M+H+].

Provenance & Evidence