Hydrochloric Acid → HCID 178504987, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-{(3-chloro-4-fluoro-benzyl)-[2-(7-methanesulfonylmethyl-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-1H-pyrrole-2-carboxylic acid allyl ester (Example 17i, 304.5 mg, 0.488 mmol) in absolute ethanol (5 mL) was added a 21% solution of sodium ethoxide in ethanol (1.1 mL, 2.95 mmol). After stirring at 60° C. for 12 h, the mixture was diluted with ethyl acetate and acidified with 1.0 M aqueous hydrochloric acid solution upon which a precipitate formed. The solid was collected by vacuum filtration to afford the desired product, N-{3-[1-(3-chloro-4-fluoro-benzyl)-4-hydroxy-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}-methanesulfonamide (88.5 mg, 0.156 mmol, 32% yield) as an off-white solid. The filtrate was extracted with ethyl acetate (2×20 mL). The combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The crude mixture was purified by HPLC purification (Column Luna 5μ C18 (2) 100 Å AXIA 150×21.2 mm, 5 micron, 25%-100% in 12 min@30 mL/min flow rate, 0.05% trifluoroacetic acid in acetonitrile/0.05% trifluoroacetic acid in water) to afford more of the desired product, N-{3-[1-(3-chloro-4-fluoro-benzyl)-4-hydroxy-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}-methanesulfonamide (18.4 mg, 0.033 mmol, 7% yield; total 39% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 3.06 (3H, s), 5.61 (2H, s), 6.57 (1H, s), 6.98 (1H, s), 7.37 (2H, d, J=7.6 Hz), 7.52 (1H, dd, J1=8.5 Hz, J2=2.4 Hz), 7.59-7.68 (4H, m), 10.17 (1H, s). LC-MS (ESI) calcd for C22H17ClFN5O6S2 565.03, found 566.2 [M+H+].

Provenance & Evidence