Tetrahydrofuran → Pyrrolo[1,2-b]pyridazine-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

A 1 mL tetrahydrofuran solution of methanesulfonyl chloride (41.9 mg, 0.366 mmol) was added to a solution of 6-bromo-4-((3aS,4R,5R,6aS)-4-methyloctahydrocyclopenta[c]pyrrol-5-ylamino)pyrrolo[1,2-b]pyridazine-3-carboxamide TFA salt (150 mg, 0.305 mmol) and N,N-diisopropylethylamine (0.266 mL, 1.523 mmol) in N,N-dimethylformamide (2 mL) at 0° C. After stirring for 1 h at 0° C., the mixture was quenched with saturated sodium bicarbonate (5 mL), diluted with ethyl acetate (80 ml), washed with water, brine, dried (MgSO4) and concentrated. The residue was purified by silica gel chromatography to provide 6-bromo-4-((3aS,4R,5R,6aS)-4-methyl-2-(methylsulfonyl)octahydrocyclopenta[c]pyrrol-5-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (105 mg, 76% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.44-11.18 (1 H, m), 8.25 (1 H, s), 7.88 (1 H, d, J=1.76 Hz), 7.13 (1 H, d, J=1.76 Hz), 3.87-4.11 (1 H, m), 3.15-3.24 (3 H, m), 3.02-3.08 (1 H, m), 2.92 (3 H, s), 2.77-2.85 (1 H, m), 2.53-2.64 (1 H, m), 2.27-2.39 (1 H, m), 1.51-1.72 (1 H, m), 1.23-1.33 (1 H, m), 1.06 (3 H, d, J=6.38 Hz); MS (ES+) m/z: 439.2, 441.2 (M+H).

Provenance & Evidence