Reaktion #2075750

Reaktionsgleichung

water

(6-chloro-2-methoxy-pyrimidin-4-yl)-[2-(2,4-dichloro-phenyl)-ethyl]-amine

3-(1-carboxy-1-methyl-ethyl)-phenyl boronic acid

HCl

→

2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid

Ausbeute 87.3%

Lösungsmittel

acetonitrile

sodium carbonate

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe reaction vessel is sealed
2. 2
   Extraktionthis mixture is extracted three times with ethyl acetate (30 mL)
3. 3
   WaschenThe combined extracts are washed with brine
4. 4
   Trocknendried over sodium sulfate
5. 5
   Einengenconcentrated

Vorschrift

A solution of (6-chloro-2-methoxy-pyrimidin-4-yl)-[2-(2,4-dichloro-phenyl)-ethyl]-amine (0.51 mmol) and 3-(1-carboxy-1-methyl-ethyl)-phenyl boronic acid (0.61 mmol) in acetonitrile (2.5 mL) and aqueous sodium carbonate solution (0.4 M, 2.5 mL) is degassed with nitrogen for 5 minutes before addition of tetrakistriphenylphosphine palladium (0) (29.5 mg, 5 mol %). The reaction vessel is sealed and heated under microwave to 130° C. for 30 minutes. To the reaction mixture is added 2 mL of water, the pH is adjusted to about 7 using 2 N aqueous HCl and this mixture is extracted three times with ethyl acetate (30 mL). The combined extracts are washed with brine, dried over sodium sulfate and concentrated. The residue is subjected to silica gel chromatography to afford 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid as a solid (205 mg, 75%). LC/MS: RT=2.39 minutes, MS: 460 (M+H); 1H NMR [300 MHz, (CD3)2SO]: δ 12.38 (1H, s), 7.36-8.00 (7H, m), 6.58 (1H, s), 3.84 (3H, s), 3.58 (2H, m), 2.98 (2H, m), 1.54 (6H, s).

Quelle