Ethanol → HCID 178515433, compound

Participants

Reaction Conditions

Reaction Steps

N,N-Dicyclohexylcarbodiimide (4.33 mL of a 1.0 M solution in dichloromethane, 4.33 mmol) was added to a solution of (7-iodo-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid (Example 4b, 1.58 g, 4.32 mmol) and 1-(4-fluoro-benzylamino)-1H-pyrrole-2-carboxylic acid allyl ester (Example 9a, 1.08 g, 3.94 mmol) in a 4:1 mixture of dichloromethane and N,N-dimethylformamide (25 mL) at 25° C. The reaction mixture was stirred at 25° C. for 2.5 h then was filtered. The filtrate was concentrated in vacuo and the residue was dissolved in ethanol (20 mL) at 25° C. A 21% solution of sodium ethoxide in ethanol (8.0 mL, 24.6 mmol) was added and the reaction mixture was heated at 80° C. for 8 h. After cooling to 25° C., the mixture was partitioned between 1.0 M aqueous hydrochloric acid solution (150 mL) and ethyl acetate (2×150 mL). The organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to give a dark solid. Trituration of this material with methanol afforded a grey solid that was collected by vacuum filtration to afford the desired product, 1-(4-fluoro-benzyl)-4-hydroxy-3-(7-iodo-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-pyrrolo[1,2-b]pyridazin-2-one (1.42 g, 2.52 mmol, 64% yield). 1H NMR (400 MHz, DMSO-d6) δ: 5.64 (2H, s), 6.58-6.60 (1H, m), 7.01-7.02 (1H, m), 7.14-7.18 (2H, m), 7.42-7.46 (2H, m), 7.70-7.70 (1H, m), 8.02-8.04 (1H, m), 8.12-8.12 (1H, m), 13.70 (1H, s).

Provenance & Evidence