反应详情

温度

110 °C

To a solution of N-[(1S,2S)-2-amino-4,4-difluorocyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide (Intermediate 46; 100 mg, 0.33 mmol) in dry toluene (3 ml) was added 2-bromo-5-(difluoromethoxy)pyridine (CAS number 845827-14-7; 89 mg, 0.33 mmol), BINAP (20 mg, 0.033 mmol), tris(dibenzylideneacetone)dipalladium(0) (15 mg, 0.016 mmol) and sodium tert-butoxide (44 mg, 0.46 mmol). The reaction was placed under an atmosphere of nitrogen, sealed and heated at 110° C. for 2.5 hours then filtered through a thiol cartridge, eluting with ethyl acetate and water. The filtrate was diluted with further ethyl acetate and water and then partitioned. The organics were washed with water, dried over magnesium sulfate, filtered and concentrated in vacuo. The crude material was purified by column chromatography (silica, 0-100% ethyl acetate/petrol) then triturated with heptane and diethyl ether to afford the title compound.

1. customsealed
2. filtrationthen filtered through a thiol cartridge
3. washeluting with ethyl acetate and water
4. additionThe filtrate was diluted with further ethyl acetate and water
5. custompartitioned
6. washThe organics were washed with water
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe crude material was purified by column chromatography (silica, 0-100% ethyl acetate/petrol)
11. customthen triturated with heptane and diethyl ether