Lithium hydroxide, monohydrate → 2-cyano-N-[2-[[6-[[5-[5-fluoro-2-(hydroxymethyl)-3-(4-oxo-6,7,8,9-tetrahydrobenzothiopheno[2,3-d]pyridazin-3-yl)phenyl]-1-methyl-2-oxo-3-pyridyl]amino]-2-pyridyl]oxy]ethyl]prop-2-enamide

Participants

Reaction Steps

To a mixture of 117b (80 mg, 0.112 mmol) in THF (5 mL) was added LiOH.H2O (10 mg, 0.224 mmol) in H2O (5 mL) to pH 10-11. The reaction mixture was stirred at rt for 4 h and concentrated. The residue was purified by prep-HPLC to give 117 (12 mg, 16%) as white solid. The amide bond was partially cleaved under basic conditions. 1H NMR (500 MHz, CDCl3): δ8.57 (s, 1H), 8.29 (s, 1H), 7.99 (bs, 1H), 7.49 (t, J=8 Hz, 2H), 7.26-7.24 (m, 1H), 7.12 (d, J=10 Hz, 1H), 6.48 (d, J=8 Hz, 1H), 6.26 (d, J=8 Hz, 1H), 4.41 (t, J=5 Hz, 2H), 4.31 (bs, 2H), 4.00-3.98 (m, 1H), 3.72 (s, 3H), 3.63 (t, J=5.5 Hz, 1H), 3.58-2.56 (m, 1H), 2.99 (t, J=5 Hz, 2H), 2.87 (t, J=5 Hz, 2H), 2.00-1.96 (m, 4H). ESI-LCMS: m/z=668.0 [C34H30FN7O5S+H]+

Provenance & Evidence