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In a 5 mL round bottom flask equipped with a magnetic stirbar and a condenser with a calcium sulfate drying tube was stirred at reflux for 18 hours a mixture of Intermediate 4D, 1-(4-((1,5-naphthyridin-2-yl)methoxy)phenyl)-2-(pyridin-4-yl)ethanone (104 mg, 0.293 mmol) and N,N-dimethylformamide dimethyl acetal (1.0 mL, 7.53 mmol). The reaction mixture was checked by TLC (95:5 EtOAc/MeOH). The spot for starting material had been replaced by a lower Rf spot. Volatiles were removed under reduced pressure to give a brown oil, 1-(4-((1,5-naphthyridin-2-yl)methoxy)phenyl)-3-(dimethylamino)-2-(pyridin-4-yl)prop-2-en-1-one (120 mg, 0.292 mmol) that was dissolved in methanol (2.5 mL) and stirred at ambient temperature. Hydrazine monohydrate (0.02127 mL, 0.438 mmol) was added via syringe and the reaction mixture was stirred at reflux for 2 hours. Another 1.5 equivalents of hydrazine monohydrate was added and stirring at reflux was continued an additional 2 hours. Volatiles were removed under reduced pressure to give a tan solid that was rinsed with water 3 times then stirred with Et2O overnight. The Et2O was decanted away and the remaining solid was partitioned between CHCl3 and brine. The aqueous layer was extracted once more with CHCl3 and the combined organic layers were dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure to give a crude, bright yellow solid. This solid was purified by column chromatography on an Analogix IF-280 (Agilent SF15-24 g, 100% DCM to 98:2 DCM/2M NH3 in MeOH). Fractions #5-20 were combined and concentrated under reduced pressure to give a pale yellow solid. The solid was dissolved in warm CHCl3 and the resulting solution was filtered and concentrated under reduced pressure. The solid residue was rinsed with Et2O, then dissolved in a minimum of hot MeOH. The solution was placed in a 0° C. freezer to induce crystallization. Intermediate 4, 2-((4-(4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl)-1,5-naphthyridine was obtained by filtration as white crystals (16.5 mg, 14.9%). 1H NMR (300 MHz, methanol-d4) δ 8.98 (dd, J=4.2, 1.6 Hz, 1H), 8.48 (dd, J=8.6, 1.8 Hz, 2H), 8.36 (dd, J=4.7, 1.6 Hz, 2H), 8.02 (d, J=8.8 Hz, 1H), 7.97 (br s, 1H), 7.82 (dd, J=8.5, 4.3 Hz, 1H), 7.42-7.36 (m, 2H), 7.33 (d, J=5.9 Hz, 2H), 7.16 (d, J=7.3 Hz, 2H), 5.47 (s, 2H). MS (ESI) m/z=380 (M+H)+.

1. customIn a 5 mL round bottom flask equipped with a magnetic stirbar and a condenser with a calcium sulfate drying tube
2. temperatureat reflux for 18 hours
3. customVolatiles were removed under reduced pressure