Tetrahydrofuran → 3-(6-(4-(tert-Butoxycarbonyl)piperazin-1-yl)pyridin-3-yl)-8-morpholinoimidazo[1,2-b]pyridazine-2-carboxylic acid

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Reaction Steps

Compound 20b (2.07 g, 3.85 mmol) was placed in a 100 mL round bottom flask equipped with a stir bar and then THF (35 mL) was added. 1M NaOH (7.7 mL) was added and the reaction was stirred at rt for 3 d. Additional 1 M NaOH (8 mL) was added followed by addition of MeOH until the reaction went homogeneous. The reaction was stirred for 4 h and then the solvent was removed under reduced pressure. The residue was dissolved in water (100 mL) and extracted with Et2O (2×20 mL). The aqueous phase was acidified with 10% citric acid resulting in a precipitate. The mixture was diluted with DCM (100 mL) and the organic phase was separated. The aqueous layer was extracted with DCM (3×50 mL) and then the combined organic extracts were washed with water (30 mL) and dried over MgSO4. The solution was filtered and the solvent was removed under reduced pressure to afford compound 20c. 1H-NMR (400 MHz, CDCl3) δ (ppm): 8.58 (d, J=2.0 Hz, 1H), 8.06 (d, J=5.6 Hz, 1H), 7.91 (dd, J=8.9, 2.3 Hz, 1H), 6.76 (d, J=8.8 Hz, 1H), 6.14 (d, J=5.9 Hz, 1H), 3.97-4.06 (m, 4H), 3.90-3.97 (m, 4H), 3.61-3.70 (m, 4H), 3.52-3.60 (m, 4H), 1.50 (s, 9H).

Provenance & Evidence