反应详情

温度

-78 °C

To a mixture of methyllithium-lithium bromide (1.5M in ether, 2.28 ml) in dry toluene (6.3 ml) at -78° under nitrogen in a flame-dried flask is added a mixture of 1-benzyl-4-[N-methyl-N-(3-(1-ethoxycyclopropylamino)-2-pyridinyl)amino]piperidine (EXAMPLE 123, 325 mg) in dry toluene (8.5 ml) at -78°. The mixture is stirred at -78° C. for 1 hr, quenched carefully with saturated aqueous ammonium chloride (10 ml) and water (10 ml) and warmed to 20°-25°. The mixture is extracted with ethyl acetate (25 ml) and the organic phase is washed with water (10 ml) and saline (10 ml), dried over magnesium sulfate and concentrated to give the crude product which is chromatographed (silica gel, 230-400 mesh, 35 g; eluting with a gradient of methanol/chloroform (1/99-4/96)) to give the title compound, NMR (CDCl3) 7.72, 7.31, 7.25, 7.17, 6.91, 5.02, 3.50, 3.02, 2.88, 2.59, 2.01, 1.71, 1.32, 0.75 and 0.65δ.

1. additionis added
2. customquenched carefully with saturated aqueous ammonium chloride (10 ml) and water (10 ml)
3. temperaturewarmed to 20°-25°
4. extractionThe mixture is extracted with ethyl acetate (25 ml)
5. washthe organic phase is washed with water (10 ml) and saline (10 ml)
6. dry with materialdried over magnesium sulfate
7. concentrationconcentrated
8. customto give the crude product which
9. customis chromatographed (silica gel, 230-400 mesh, 35 g
10. washeluting with a gradient of methanol/chloroform (1/99-4/96))