Acetaldehyde → 2-(4-ethylpiperazin-1-yl)-5,7-difluoro-3-methyl-N-(5-morpholinopyridin-3-yl)quinolin-4-amine

Participants

Reaction Steps

The 5,7-difluoro-3-methyl-N-(5-morpholinopyridin-3-yl)-2-(piperazin-1-yl)-quinolin-4-amine (50 mg, 0.11 mmol) was dissolved in a mixture of dichloroethane (1.3 mL) and MeOH (0.63 mL). The acetaldehyde (6.4 μL, 0.11 mmol) and sodium triacetoxyborohydride (72 mg, 0.34 mmol) were added and the mixture was stirred overnight. A small amount (50 mg) of sodium cyanoborohydride was added to drive the reaction to completion. The reaction was quenched with satd sodium bicarbonate solution and extracted with EtOAc. The organic layer was then dried over magnesium sulfate and the filtrate was cond. The crude material was purified by reverse-phase preparative HPLC using a Phenomenex Gemini™ column, 10 micron, C18, 100 Å, 150×30 mm, 0.1% TFA in CH3CN/H2O, gradient 10% to 95% over 20 min to provide 2-(4-ethylpiperazin-1-yl)-5,7-difluoro-3-methyl-N-(5-morpholinopyridin-3-yl)quinolin-4-amine. The salt was then free based by eluting through an SCX column with 0 to 2M ammonia in MeOH to give the desired product as the free base. TFA salt: 1H NMR (CDCl3) δ ppm 7.86 (2H, dd, J=4.3, 2.2 Hz), 7.61 (1H, d, J=9.2 Hz), 7.36-7.43 (1H, m), 7.20 (1H, t, J=2.0 Hz), 6.89 (1H, ddd, J=13.4, 8.5, 2.3 Hz), 4.24 (2H, d, J=14.7 Hz), 3.86-3.95 (4H, m), 3.77 (2H, t, J=13.2 Hz), 3.63 (2H, d, J=12.3 Hz), 3.26-3.38 (4H, m), 3.15 (4H, q, J=7.2 Hz), 2.13 (3H, s), 1.39 (3H, t, J=7.3 Hz). Mass Spectrum (ESI) m/e=469.3 (M+1).

Provenance & Evidence