反应详情

To a stirred suspension of 3-amino-6-bromo-5-trifluoromethyl-pyridine-2-carboxylic acid (2-hydroxy-2-methyl-propyl)-amide (Ex. 1.10) (180 mg, 0.505 mmol) and 4-fluorophenylboronic acid (106 mg, 0.758 mmol) in a 2:1 mixture of toluene:EtOH (12 ml) under nitrogen was added 2M Na2CO3(aq) (1.011 ml, 2.022 mmol) followed by Pd(dppf)Cl2.CH2Cl2 adduct (41 mg, 0.051 mmol). The reaction mixture was heated using microwave radiation at 140° C. for 1 hour and then allowed to cool to RT. The mixture was diluted with EtOAc (100 ml) and washed with water (100 ml). The organic phase was separated, filtered through Celite® (filter material) dried (MgSO4) and concentrated in vacuo to yield a brown oil/solid. Purification by chromatography on silica eluting with MeOH/DCM yielded a yellow oil/solid. This was passed through a 500 mg Isolute® Si-TMT cartridge (2,4,6-trimercaptotriazine silica, pre-wetted with DCM) eluting with 30% MeOH/DCM (50 ml) to afford a yellow oil/solid. The crude product was dried in vacuo and slurried in ˜0.5 ml DCM. The resulting suspension was removed by filtration and the filtrate was evaporated to yield the title compound as a light yellow/brown foam-like solid; LC-MS Rt=5.30 mins [M+H]+ 372 (Method 10minLC_v002).

1. temperatureThe reaction mixture was heated
2. customat 140° C.
3. customfor 1 hour
4. washwashed with water (100 ml)
5. customThe organic phase was separated
6. filtrationfiltered through Celite® (filter material)
7. dry with materialdried (MgSO4)
8. concentrationconcentrated in vacuo
9. customto yield a brown oil/solid
10. customPurification by chromatography on silica eluting with MeOH/DCM
11. customyielded a yellow oil/solid
12. washeluting with 30% MeOH/DCM (50 ml)
13. customto afford a yellow oil/solid
14. dry with materialThe crude product was dried in vacuo
15. customThe resulting suspension was removed by filtration
16. customthe filtrate was evaporated