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

Temperature

0 °C

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).

1. customthe mixture was quenched with saturated sodium bicarbonate (5 mL)
2. additiondiluted with ethyl acetate (80 ml)
3. washwashed with water, brine
4. dry with materialdried (MgSO4)
5. concentrationconcentrated
6. customThe residue was purified by silica gel chromatography

ORD record

ord-d0dba9a3a80f4e78bc4f422dcd891b61

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08987268B2