Ammonium Chloride → HCID 66600223, compound

Participants

Reaction Steps

Lithium bis(trimethylsilyl)amide (1.0 M solution in hexane, 0.592 mL, 0.592 mmol) was added to a solution of 6-(2-fluoro-5-(1-(4-morpholinyl)ethyl)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-2-methyl-4-pyrimidinamine (0.110 g, 0.197 mmol) and 5-fluoro-6-methoxypyridin-3-amine (0.042 g, 0.296 mmol, Anichem, North Brunswick, N.J.) in THF (1.5 mL) at −10° C. After 1 h, more lithium bis(trimethylsilyl)amide (1.0 M solution in hexane, 0.592 mL, 0.592 mmol) and 5-fluoro-6-methoxypyridin-3-amine (0.042 g, 0.296 mmol) were added. After a further 1 h, saturated NH4Cl (aq.) was added. The mixture was extracted with EtOAc (3×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The crude material was adsorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g), eluting with a gradient of 0% to 100% EtOAc in hexane to give 6-(2-((5-fluoro-6-methoxy-3-pyridinyl)amino)-5-(1-(4-morpholinyl)ethyl)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-2-methyl-4-pyrimidinamine (0.104 g, 0.153 mmol, 78% yield) as a brown oil. 1H NMR (400 MHz, CDCl3) δ 11.92 (s, 1H); 8.26 (dd, J=12.72, 2.35 Hz, 1H); 8.11 (d, J=2.15 Hz, 1H); 8.02 (d, J=2.35 Hz, 1H); 7.56-7.61 (m, 1H); 7.18 (dd, J=8.61, 0.98 Hz, 4H); 6.82-6.91 (m, 4H); 6.53 (s, 1H); 4.80 (br s, 4H); 4.01 (s, 3H); 3.79 (s, 6H); 3.62 (t, J=4.69 Hz, 4H); 3.30 (q, J=6.65 Hz, 1H); 2.66 (s, 3H); 2.39-2.47 (m, 2H); 2.30-2.37 (m, 2H); 1.31 (d, J=6.85 Hz, 3H). m/z (ESI, +ve) 680.2 (M+H)+.

Provenance & Evidence