Reaktion #325933

Reaktionsgleichung

(R)-1-cyclopentyl-3-(1-(4-fluoro-3-(trifluoromethyl)phenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)urea

N-methylcyclopentanamine

→

(R)-1-cyclopentyl-3-(1-(4-fluoro-3-(trifluoromethyl)phenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-1-methylurea

Ausbeute 65.0%

Lösungsmittel

DMSO THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   FiltrationThe reaction mixture was filtered
2. 2
   Waschenthe solid was washed with EtOAc
3. 3
   WaschenThe filtrate was then washed with H2O, sat. NaCl
4. 4
   Trocknendried over Na2SO4
5. 5
   SonstigeThe organic solvent was evaporated under reduced pressure
6. 6
   Sonstigethe resulting residue was purified by prep HPLC (Phenomenex AXIA Luna 75×30 mm, 5μ column eluting with 10-90% ACN/H2O over 10 minutes containing 0.1% TFA; 40 mL/min, monitoring at 220 nm)

Vorschrift

To a solution of (R)-1-cyclopentyl-3-(1-(4-fluoro-3-(trifluoromethyl)phenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)urea (20 mg, 0.033 mmol), prepared as described in Procedure 3, 4, 5, 6 and 2, in DMSO/THF (0.1 mL/0.1 mL) was added N-methylcyclopentanamine (32 mg, 0.33 mmol). The resulting solution was stirred at 120° C. under microwave irradiation for 1800 sec. The reaction mixture was filtered and the solid was washed with EtOAc. The filtrate was then washed with H2O, sat. NaCl and dried over Na2SO4. The organic solvent was evaporated under reduced pressure and the resulting residue was purified by prep HPLC (Phenomenex AXIA Luna 75×30 mm, 5μ column eluting with 10-90% ACN/H2O over 10 minutes containing 0.1% TFA; 40 mL/min, monitoring at 220 nm) to afford (R)-1-cyclopentyl-3-(1-(4-fluoro-3-(trifluoromethyl)phenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-1-methylurea (Example 246) as white lyophillate (13 mg, 65% yield). LCMS: [M+H] 619.2 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm).

Quelle