Ammonium Chloride → 6-(2-((5-fluoro-6-methoxy-3-pyridinyl)amino)-5-((1R)-1-((2S)-2-methyl-4-(methylsulfonyl)-1-piperazinyl)ethyl)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-2-methyl-4-pyrimidinamine

Participants

Reaction Conditions

Reaction Steps

A solution of 6-(2-fluoro-5-((1R)-1-((2S)-2-methyl-4-(methylsulfonyl)-1-piperazinyl)ethyl)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-2-methyl-4-pyrimidinamine (0.130 g, 0.200 mmol) and 5-fluoro-6-methoxypyridin-3-amine (0.043 g, 0.301 mmol) in THF (2.00 mL) at −10° C. was treated with lithium bis(trimethylsilyl)amide (1.0 M solution in THF) (0.60 mL, 0.60 mmol). After 30 minutes, more lithium bis(trimethylsilyl)amide, (1.0 M solution in THF) (0.60 mL, 0.60 mmol) was added and the reaction mixture stirred for another 30 minutes at −10° C. Saturated NH4Cl (aq.) was added and the mixture was extracted with CH2Cl2 (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 silica gel column (4 g), eluting with a gradient of 0% to 100% EtOAc in hexane, to provide 6-(2-((5-fluoro-6-methoxy-3-pyridinyl)amino)-5-((1R)-1-((2S)-2-methyl-4-(methylsulfonyl)-1-piperazinyl)ethyl)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-2-methyl-4-pyrimidinamine (0.050 g, 0.065 mmol, 32.4% yield) as a brown oil. m/z (ESI, +ve) 771.2 (M+H)+.

Provenance & Evidence