Sodium ethoxide → cis-N-{3-[1-(4-chloro-benzyl)-4-hydroxy-2-oxo-2,4a,5,6,7,7a-hexahydro-1H-[1]pyrindin-3-yl]-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide

Participants

Reaction Conditions

Reaction Steps

A solution of the crude 2-{(4-chloro-benzyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclopentanecarboxylic acid ethyl ester in ethanol (20 mL) was treated with a 21% w/w solution of sodium ethoxide in ethanol (0.648 g) and stirred for 16 h at 60° C. Upon cooling, the reaction mixture was then quenched with 1.0 M aqueous hydrochloric acid solution (20 mL) and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered, and dried in vacuo. The residue was purified by prep-HPLC [Column ODS-A 5μ 100 Å, 150×21.2 mm, 5 micron, 50%-100% in 13.5 min @ 22 mL/min flow rate, 0.05% trifluoroacetic acid in acetonitrile/0.05% trifluoroacetic acid in water] to afford the desired product, cis-N-{3-[1-(4-chloro-benzyl)-4-hydroxy-2-oxo-2,4a,5,6,7,7a-hexahydro-1H-[1]pyrindin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide (72.1 mg, 0.131 mmol, 26.2% over two steps), as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 1.44-1.62 (4H, m), 1.91-2.18 (3H, m), 3.06 (3H, s), 3.78-3.94 (1H, m), 4.39-4.62 (1H, m), 4.90 (1H, d, J=15.6 Hz), 7.35-7.64 (7H, m), 10.19 (1H, s). LC-MS (ESI) calcd for C23H23ClN4O6S2 550.07, found 551.4 [M+H+].

Provenance & Evidence