Triethylamine → 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

Participants

Reaction Conditions

Reaction Steps

A solution of 6-(2-fluoro-5-((1R)-1-((2S)-2-methyl-1-piperazinyl)ethyl)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-2-methyl-4-pyrimidinamine (0.200 g, 0.350 mmol) in CH2Cl2 (3 mL) at −20° C. was treated with NEt3 (0.488 mL, 3.50 mmol) followed by methanesulfonyl chloride (0.083 mL, 1.051 mmol). The mixture stirred at −20° C. for 30 minutes. 1 M NaOH (aq.) and CH2Cl2 were then added. The layers were separated and the aqueous layer was extracted with CH2Cl2 (2×). 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 (12 g), eluting with a gradient of 60% to 100% EtOAc in hexane, to provide 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, 57.2% yield) as a white foam. m/z (ESI, +ve) 649.2 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 8.42 (dd, J=9.29, 2.45 Hz, 1H); 8.14 (d, J=1.17 Hz, 1H); 7.18 (d, J=7.82 Hz, 4H); 6.81-6.89 (m, 5H); 4.74 (br. s., 4H); 4.04 (q, J=6.78 Hz, 1H); 3.79 (s, 6H); 3.28-3.37 (m, 1H); 3.16-3.24 (m, 1H); 3.12 (dd, J=10.95, 2.93 Hz, 1H); 2.85-3.01 (m, 2H); 2.77 (s, 3H); 2.63-2.70 (m, 2H); 2.62 (s, 3H); 1.44 (d, J=6.85 Hz, 3H); 1.10 (d, J=6.26 Hz, 3H).

Provenance & Evidence