1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 178446174, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 6-cyano-4-hydroxy-1-(3-methyl-butyl)-2-oxo-1,2-dihydro-pyrrolo[1,2-b]pyridazine-3-carboxylic acid ethyl ester (Example 15e, 0.25 g, 0.788 mmol) and 2-amino-5-methanesulfonylamino-benzenesulfonamide (Example 3d, 0.209 g, 0.788 mmol) in pyridine (4 mL) was heated to 120° C. for 3 h. 1,8-Diazabicyclo[5.4.0]undec-7-ene (200 μL) was added and the mixture was heated at 120° C. for 16 h. The reaction mixture was passed through a plug of silica gel and eluted with 50%→100% ethyl acetate in hexanes. The solvents were removed in vacuo and purification by preparative HPLC (Column Luna 5μ C18 (2) 100 Å size 150×21.2 mm, 5 micron, 40%-95% in 11 min 25 mL/min flow rate, 0.05% trifluoroacetic acid in acetonitrile/0.05% trifluoroacetic acid in water) afforded the desired product, N-{3-[6-cyano-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[1,2,4]thiadiazin-7-yl}-methanesulfonamide (0.0275 g, 0.0531 mmol, 6.7% yield). 1H NMR (400 MHz, DMSO-d6) δ: 0.94 (3H, s), 0.96 (3H, s), 1.17-1.23 (2H, m), 1.51-1.57 (2H, m), 1.65-1.75 (1H, m), 5.74 (1H, s), 3.05 (3H, s), 7.40 (1H, s), 7.49-7.57 (3H, m), 8.51 (1H, s), 10.12 (1H, s), 13.75 (1H, s). LC-MS (ESI) calcd for C21H22N6O6S2 518.10. found 519.4 [M+H+].

Provenance & Evidence