Triethylamine → 2-[(E)-1-[3-[1-(6-fluoro-1-methylindazol-5-yl)ethyl]imidazo[1,2-b]pyridazin-6-yl]ethylideneamino]oxyethanol

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-(3-(1-(6-fluoro-1-methyl-1H-indazol-5-yl)ethyl)imidazo[1,2-b]pyridazin-6-yl)ethanone (100 mg, 0.267 mmol) in methanol (10 mL) was added 2-(aminooxy)ethanol hydrochloride (30.3 mg, 0.267 mmol). Triethyl amine was added dropwise to adjust the pH to 5˜6. The reaction mixture was stirred at 30° C. for 20 h. The solvent was removed in vacuo and the residue was dissolved in DCM, washed with NaHCO3 (aq) and brine. The organic layer was dried over Na2SO4 and concentrated in vacuo to afford the crude product which was purified by chromatography on silica gel to afford 19 mg (17%) of the title compound. 1H-NMR (400 MHz, DMSO-d6) δ ppm 8.01 (d, 1H), 7.91 (s, 1H), 7.77 (s, 1H), 7.58 (d, 1H), 7.50 (s, 1H), 7.49 (d, 1H), 4.91 (q, 1H), 4.76 (t, 1H), 4.20 (t, 2H), 3.95 (s, 3H), 3.65 (m, 2H), 2.13 (s, 3H), 1.76 (d, 3H). LCMS (method B): [MH]+=397, tR=2.50 min. Chiral separation (method K) provided enantiomeric pure compounds example 39-R and example 39-S.

Provenance & Evidence