Reaktion #45350

Reaktionsgleichung

Na2CO3

Methyl[3-iodo-5-(trifluoromethyl)benzyl]{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate

pyridine-4-boronic acid

dimethyl ethylene glycol

→

Methyl{[5 ′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}[3-pyridin-4-yl-5-(trifluoromethyl)benzyl]carbamate

Lösungsmittel

water

ethanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe solution was degassed with nitrogen for 2 minutes
2. 2
   Sonstigethe solution was degassed with nitrogen again for 2 minutes
3. 3
   SonstigeThe solution was sealed
4. 4
   Sonstigeplaced in a microwave reactor
5. 5
   Sonstigereached 150° C.
6. 6
   workup.WAITthe temperature was held at 150° C. for twenty minutes
7. 7
   workup.ADDITIONpoured into H2O (10 mL)
8. 8
   Extraktionextracted with EtOAc (30 mL)
9. 9
   WaschenThe organic layer was washed with brine (10 mL)
10. 10
    Trocknendried over Na2SO4
11. 11
    Filtrationfiltered
12. 12
    Einengenconcentrated
13. 13
    SonstigePurification by flash chromatography with 5% to 80% EtOAc/hexanes
14. 14
    Sonstigeafforded methyl{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl)}[3-pyridin-4-yl-5-(trifluoromethyl)benzyl]carbamate

Vorschrift

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).

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