Triethylamine → 6-(2-fluoro-5-((1R)-1-(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-(1-piperazinyl)ethyl)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-2-methyl-4-pyrimidinamine (0.448 g, 0.805 mmol) in CH2Cl2 (4 mL) at −20° C. was treated with NEt3 (1.122 mL, 8.05 mmol) followed by methanesulfonyl chloride (0.190 mL, 2.414 mmol). The mixture stirred at −20° C. for 30 minutes and then 1 M NaOH (aq.) and CH2Cl2 were added. The layers were separated and the aqueous layer was extracted with CH2Cl2 (2×). 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 75% to 100% EtOAc in hexane, to provide 6-(2-fluoro-5-((1R)-1-(4-(methylsulfonyl)-1-piperazinyl)ethyl)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-2-methyl-4-pyrimidinamine (0.317 g, 0.499 mmol, 62.1% yield) as a white foam. m/z (ESI, +ve) 635.2 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 8.46 (d, J=9.00 Hz, 1H); 8.18 (s, 1H); 7.17 (d, J=7.63 Hz, 4H); 6.83-6.89 (m, 5H); 4.74 (br. s., 4H); 3.80 (s, 6H); 3.65 (m, 1H); 3.18-3.30 (m, 4H); 2.77 (s, 3H); 2.64 (s, 5H); 2.50-2.58 (m, 2H); 1.44 (d, J=6.65 Hz, 3H).

Provenance & Evidence