Reaktion #497717

Reaktionsgleichung

2-chloro-4-(trifluoromethyl)pyrimidine

product

{5-[3-amino-5-(morpholin-4-yl)phenyl]-1,3-thiazol-2-yl}(dicyclopropyl)methanol

cesium carbonate

XantPhos

→

dicyclopropyl{5-[3-(morpholin-4-yl)-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl]-1,3-thiazol-2-yl}methanol

Ausbeute 54.0%

Lösungsmittel

water

dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturAfter cooling to room temperature
2. 2
   Filtrationthe reaction mixture was filtered through a celite column with dichloromethane
3. 3
   EinengenThe filtrate was concentrated
4. 4
   Sonstigethe residue was purified by chromatography on silica gel (0-100% ethyl acetate in hexanes)
5. 5
   SonstigeThe yellow residue was triturated in diethyl ether (with trace dichloromethane)

Vorschrift

To a solution of 2-chloro-4-(trifluoromethyl)pyrimidine (0.079 mL, 0.654 mmol) and the product of Step 5 (221 mg, 0.595 mmol) in dioxane (4.0 mL) was added cesium carbonate (388 mg, 1.190 mmol), Pd(OAc)2 (6.68 mg, 0.030 mmol) and XantPhos (51.6 mg, 0.089 mmol) and the mixture was heated to 125° C. for 2 hours. After cooling to room temperature, 1.5 mL of water was added and the reaction mixture was filtered through a celite column with dichloromethane. The filtrate was concentrated and the residue was purified by chromatography on silica gel (0-100% ethyl acetate in hexanes). The yellow residue was triturated in diethyl ether (with trace dichloromethane) to give dicyclopropyl{5-[3-(morpholin-4-yl)-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl]-1,3-thiazol-2-yl}methanol (165 mg, 0.319 mmol, 54% yield) as an off-white solid. MS APCI: [M+H]+ m/z 518.1. 1H NMR (400 MHz, DMSO-d6): δ 10.17 (s, 1H); 8.84 (d, J=4.9 Hz, 1H); 7.98 (s, 1H); 7.57 (s, 1H); 7.40 (s, 1H); 7.28 (d, J=4.9 Hz, 1H); 6.89 (s, 1H); 5.38 (s, 1H); 3.77 (t, J=4.3 Hz, 4H); 3.17 (t, J=4.4 Hz, 4H); 1.41-1.33 (m, 2H); 0.54-0.38 (m, 6H); 0.32-0.24 (m, 2H). rhSYK activity=+++

Quelle