2-Chloropyrimidine → N-{[4-(4-[(1-isopropylpiperidin-4-yl)oxy]phenyl)tetrahydro-2H-pyran-4-yl]methyl}pyrimidin-2-amine

Participants

Reaction Conditions

Reaction Steps

A mixture of (4-{4-[(1-isopropylpiperidin-4-yl)oxy]phenyl}tetrahydro-2H-pyran-4-yl)methylamine (150 mg, 0.422 mmol), 2-chloropyrimidine (52 mg, 0.422 mmol) and N,N-diisopropylethylamine (161 μl, 0.904 mmol) in N-methylpyrrolidinone (0.5 ml) was heated at 150° C. in the microwave (Smith Personal Synthesiser) for 900 seconds. The reaction mixture was partitioned between ethyl acetate (10 ml) and saturated NaHCO3 (10 ml). The organic washings were dried over Na2SO4 and concentrated in vacuo to give an orange oil. The compound was purified by column chromatography on silica gel, eluting with dichloromethane:methanol:ammonia, 100:0:0 to 96:4:0.4, to give the title compound as a solid (87 mg, 47%). 1H NMR (400 MHz, CDCl3) δ 8.20 (d, 2H), 7.21 (d, 2H), 6.90 (d, 2H), 6.48 (t, 2H), 4.71 (m, 1H), 4.20-4.35 (broad, 1H), 3.80-3.90 (m, 2H), 3.55-3.70 (multiple peaks, 4H), 2.70-2.90 (m, 3H), 2.32-2.49 (m, 2H), 1.78-2.19 (several multiplets, 8H), 1.10 (d, 6H).

Provenance & Evidence