反应详情

Methyl[3-iodo-5-(trifluoromethyl)benzyl]{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate (Example 119, 20 mg, 0.03 mmol) and pyridine-4-boronic acid (4.6 mg, 0.04 mmol) were placed in a microwave tube in a microwave tube, and dissolved with dimethyl ethylene glycol (170 μL). Next, 2M Na2CO3 (38 μL), ethanol (42 μL), and water (56 μL) were added. The solution was degassed with nitrogen for 2 minutes. Pd(PPh3)4 (3.5 mg, 0.003 mmol) was added and the solution was degassed with nitrogen again for 2 minutes. The solution was sealed and placed in a microwave reactor. The wattage was set for 60 W until the temperature reached 150° C. and then the temperature was held at 150° C. for twenty minutes. The mixture was then cooled to room temperature, poured into H2O (10 mL), and extracted with EtOAc (30 mL). The organic layer was washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated. Purification by flash chromatography with 5% to 80% EtOAc/hexanes afforded methyl{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl)}[3-pyridin-4-yl-5-(trifluoromethyl)benzyl]carbamate. Rf=0.40 (75% EtOAc/hexanes). LCMS=617.3 (M+1)+. 1H NMR (C6D6, 500 MHz, 70° C.) δ 8.54 (broad singlet, 2H), 7.70 (s, 1H), 7.51 (s, 1H), 7.38 (s, 1H), 7.35 (d, J=8.0, 1H), 7.28 (s, 1H), 7.06 (d, J=8.0, 1H), 7.02 (dd, J=2.0 Hz, 8.5, 1H), 6.89 (m, 2H), 6.83 (d, J=2.0, 1H), 6.58 (d, J=8.5, 1H), 4.45 (broad singlet, 2H), 4.13 (broad singlet, 2H), 3.38 (s, 3H), 3.23 (s, 3H), 2.65 (m, 1H), 1.12 (d, J=7.0 Hz, 6H).

1. customThe solution was degassed with nitrogen for 2 minutes
2. customthe solution was degassed with nitrogen again for 2 minutes
3. customThe solution was sealed
4. customplaced in a microwave reactor
5. customreached 150° C.
6. waitthe temperature was held at 150° C. for twenty minutes
7. additionpoured into H2O (10 mL)
8. extractionextracted with EtOAc (30 mL)
9. washThe organic layer was washed with brine (10 mL)
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated
13. customPurification by flash chromatography with 5% to 80% EtOAc/hexanes
14. customafforded methyl{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl)}[3-pyridin-4-yl-5-(trifluoromethyl)benzyl]carbamate