反应详情

5-Amino-3-methyl-2(pyridin-2-ylmethyloxy)pyridine (D15, 0.5 g, 2.3 mmol) in dichloromethane (30 ml) was cooled to −20° C. under argon. Triethylamine (0.32 ml, 2.3 mmol) was added, followed dropwise by phenyl chloroformate (0.35 ml, 2.8 mmol). The mixture was warmed to room temperature and diluted with dichloromethane (100 ml) then washed with aqueous sodium bicarbonate (50 ml), dried (Na2SO4) and evaporated in vacuo to give phenyl N-2-[3-methyl-(pyridin-2-ylmethyloxypyridin-5-yl]carbamate. The crude carbamate was treated with 5-methyl-6-trifluoromethylindoline (D7, 0.47 g, 0.0023 mol, 1 eq) and triethylamine (1 ml) in DMF (30 ml) at 100° C. under argon for 2 hours then allowed to cool. Solvent was removed in vacuo and the residue was partitioned between dichloromethane (3×100 ml) and 10% aqueous sodium hydroxide (50 ml). The combined organics were dried (Na2SO4) and evaporated in vacuo to give the crude product which was subjected to flash chromatography using 5% methanol/dichloromethane as eluant and recrystallised from dichloromethane/60-80° C. petroleum ether to afford the title compound (0.27 g, 28%) as white crystals. m.p. 188-189° C.

1. washthen washed with aqueous sodium bicarbonate (50 ml)
2. dry with materialdried (Na2SO4)
3. customevaporated in vacuo
4. customto give phenyl N-2-[3-methyl-(pyridin-2-ylmethyloxypyridin-5-yl]carbamate
5. temperatureto cool
6. customSolvent was removed in vacuo
7. customthe residue was partitioned between dichloromethane (3×100 ml) and 10% aqueous sodium hydroxide (50 ml)
8. dry with materialThe combined organics were dried (Na2SO4)
9. customevaporated in vacuo
10. customto give the crude product which
11. customrecrystallised from dichloromethane/60-80° C. petroleum ether