Triethylamine → N-[2-[3-(2,2-dimethylpropanoylamino)-4-methyl-phenyl]imidazo[2,1-f]pyridazin-6-yl]-3-[3-oxo-3-(tetrahydropyran-2-yloxyamino)prop-1-enyl]benzamide

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Reaction Steps

A 20-mL vial is charged with acetonitrile (0.4 mL), 3-[3-[[2-[3-(2,2-dimethylpropanoylamino)-4-methyl-phenyl]imidazo[2,1-f]pyridazin-6-yl]carbamoyl]phenyl]prop-2-enoic acid (0.025 g, 0.05 mmol), O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (0.0088 g, 0.08 mmol), triethylamine (0.021 mL, 0.15 mmol) and (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (0.033 g, 0.08 mmol). The mixture is stirred at room temperature for 2 hr, concentrated and taken up into saturated aqueous Na2CO3 (2 mL), extracted with EtOAc and CH2Cl2. Organic layers are combined, dried and concentrated to give crude N-[2-[3-(2,2-dimethylpropanoylamino)-4-methyl-phenyl]imidazo[2,1-f]pyridazin-6-yl]-3-[3-oxo-3-(tetrahydropyran-2-yloxyamino)prop-1-enyl]benzamide. This is taken up in a mixture of aqueous HCl (1 mL, 1M) and MeOH (1 mL), and is stirred at 50° C. for 1 hour. The mixture is concentrated, taken up in DMSO (1 mL) and purified on a Gilson preparative HPLC (reverse phase) to afford the title compound (0.015 g). LCMS (m/z)=513.5 [M+H]+, tR=2.31 min.

Provenance & Evidence