Ethanol → HCID 135936705, compound

Participants

Reaction Conditions

Reaction Steps

[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; 0.108 g, 0.306 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.128 g, 0.337 mmol) and 4-methylmorpholine (0.067 mL, 0.609 mmol) were added sequentially to a solution of rac-2-benzyl-3-(4-fluoro-benzylamino)-propionic acid ethyl ester (0.096 g, 0.304 mmol) in N,N-dimethylformamide (4 mL) at 25° C. The reaction mixture was stirred at 25° C. for 18 h, and then was concentrated in vacuo. The residue was partitioned between 1.0 M aqueous hydrochloric acid solution (100 mL) and ethyl acetate (2×100 mL). The organic layers were dried over sodium sulfate and were concentrated in vacuo. The residue was dissolved in ethanol (4 mL) at 25° C. A 21 wt. % solution of sodium ethoxide in ethanol (0.394 mL, 1.22 mmol) was added and the reaction mixture was heated to 60° C. for 20 h. After cooling to 25° C., the reaction mixture was partitioned between 1.0 M aqueous hydrochloric acid solution (100 mL) and ethyl acetate (2×100 mL). The organic layers were dried over sodium sulfate and were concentrated in vacuo. The residue was purified by flash chromatography (Teledyne Isco RediSep column; 50-100% ethyl acetate in hexanes) to afford (after trituration with diethylether) rac-N-{3-[5-benzyl-1-(4-fluoro-benzyl)-4-hydroxy-2-oxo-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 (0.058 g, 0.096 mmol, 32%) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ: 2.46 (1H, d, J=11.1 Hz), 2.69-2.78 (1H, m), 2.92-2.98 (1H, m), 2.95 (3H, s), 3.01 (1H, d, J=3.9 Hz), 3.28-3.32 (1H, m), 4.24 (2H, d, J=5.5 Hz), 4.37 (1H, d, J=13.9 Hz), 4.66 (1H, d, J=14.9 Hz), 6.88-6.90 (2H, m), 7.13-7.20 (5H, m), 7.28-7.31 (2H, m), 7.58 (1H, t, J=6.3 Hz). LC-MS (ESI) calculated for C26H25FN4O6S3 604.09. found 605.4 [M+H+].

Provenance & Evidence