Reacción #45348

Ecuación de reacción

H2O

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

methanesulfonyl chloride

N,N-diisopropylethylamine

→

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

Disolventes

CH2Cl2

Condiciones de reacción

Tratamiento posterior

1. 1
   ExtracciónThe mixture was extracted with EtOAc (50 μL)
2. 2
   Lavadothe organic extracts were washed with brine (10 mL)
3. 3
   Secadodried over Na2SO4
4. 4
   Filtraciónfiltered
5. 5
   Concentraciónconcentrated
6. 6
   OtroPurification by preparative thin layer chromatography with 25% EtOAc/hexanes
7. 7
   Otroa third and final purification by silica gel chromatography with 2% to 25% EtOAc/hexanes

Procedimiento

To a solution of methyl[3-amino-5-(trifluoromethyl)benzyl]{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate (8 mg, 0.014 mmol) (Example 33) and methanesulfonyl chloride (3.3 μL, 0.043 mmol) in CH2Cl2 (1 mL) was added N,N-diisopropylethylamine (15 μL, 0.086 mmol). The reaction was stirred at room temperature for thirty minutes and then was poured into H2O (10 mL). The mixture was extracted with EtOAc (50 μL), and the organic extracts were washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated. Purification by preparative thin layer chromatography with 25% EtOAc/hexanes followed by a preparative thin layer chromatography in 2:2:1 (CH2Cl2:Hex:Et2O) and then a third and final purification by silica gel chromatography with 2% to 25% EtOAc/hexanes afforded methyl{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}[3-[(methylsulfonyl)amino]-5-(trifluoromethyl)benzyl]carbamate. Rf=0.40 (25% EtOAc/hexanes). 1H NMR (C6D6, 500 MHz, 70° C.) δ 7.69 (s, 1H), 7.52 (s, 1H), 7.38-7.25 (m, 3H), 7.08-7.04 (m, 2H), 6.86 (s, 1H), 6.30 (d, J=8.5 Hz, 1H), 4.40 (broad singlet, 2H), 4.04-3.99 (m, 2H), 3.33 (s, 3H), 3.26 (s, 3H), 2.74 (m, 1H), 2.67 (s, 3H), 1.22 (d, J=6.5 Hz, 6H).

Fuente