Diisopropylethylamine → 5-Ethyl-2-[4-({[4'-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinyl]pyrimidine

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine hydrochloride (70 mg, 0.18 mmol), 2-chloro-5-ethylpyrimidine (30 μL, 0.24 mmol) and diisopropylethylamine (0.10 mL, 0.55 mmol) in NMP (3 mL) was heated at 80° C. overnight. After more 2-chloro-5-ethylpyrimidine (0.1 mL) was added, the reaction mixture was heated at 80° C. for 4 h. The mixture was cooled to ambient temperature, and was diluted with EtOAc, washed with water and brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as a brown oil. The crude product was purified by chromatography on a silica gel column eluted with 50% EtOAc/hexane followed by trituration with hot hexanes containing 1% MeOH to give 28 mg (34%) of the title compound as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.18 (bs, 2H), 7.96 (d, 2H, J=8.3 Hz), 7.72 (d, 2H, J=8.5 Hz), 7.54 (d, 2H, J=8.8 Hz), 6.99 (d, 2H, J=8.8 Hz), 4.85-4.70 (m, 2H), 3.88 (d, 2H, J=6.3 Hz), 3.08 (s, 3H), 3.00-2.85 (m, 2H), 2.55-2.40 (m, 2H), 2.20-2.05 (m, 1H), 2.00-1.90 (m, 2H), 1.45-1.30 (m, 2H), 1.19 (t, 3H, J=7.5 Hz); LRMS (ESI), m/z 452 (M+H).

Provenance & Evidence