Hydrochloric Acid → N-[3-(4-hydroxy-1-isopentyl-2-oxo-pyrrolo[1,2-b]pyridazin-3-yl)-1,1-dioxo-4H-1$l^{6},4-benzothiazin-7-yl]methanesulfonamide

Participants

Reaction Conditions

Reaction Steps

Crude 1-[[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,4]thiazin-3-yl)-acetyl]-(3-methyl-butyl)-amino]-1H-pyrrole-2-carboxylic acid allyl ester (Example 16a, 0.3 mmol) was dissolved in ethanol (3 mL). A 21% solution of sodium ethoxide in ethanol (0.448 mL, 1.2 mmol) was added into the above solution. The mixture was stirred at 60° C. for 4 h. Upon cooling to 25° C., the mixture was poured into 1.0 M aqueous hydrochloric acid solution (50 mL). The aqueous layer was extracted with ethyl acetate (2×50 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo to afford a yellow solid. Purification by flash column chromatography (Teledyne Isco RediSep; 20% ethyl acetate in hexanes to 100% ethyl acetate in hexanes) afforded the desired product, N-{3-[4-hydroxy-1-(3-methyl-butyl)-2-oxo-1,2-dihydro-pyrrolo[1,2-b]pyridazin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,4]thiazin-7-yl}-methanesulfonamide (20 mg, 0.04 mmol, 13% yield over two steps) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ: 1.05 (6H, d, J=6.6 Hz), 1.64-1.81 (3H, m), 3.11 (3H, s), 4.24-4.31 (2H, m), 5.53 (1H, s), 6.41-6.46 (1H, m), 6.97-7.10 (3H, m), 7.30-7.33 (1H, m), 7.60-7.64 (1H, m), 7.70-7.72 (1H, m). LC-MS (ESI) calcd for C21H24N4O6S2 492.11. found 493.3 [M+H+].

Provenance & Evidence