Reaktion #2179493

Reaktionsgleichung

6-methyl-N5-(3-(pyrimidin-4-yl)pyridin-2-yl)isoquinoline-1,5-diamine

2-bromo-1-methyl-4-(trifluoromethyl)benzene

4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene

cesium carbonate

sodium carbonate

→

6-methyl-N1-(2-methyl-5-(trifluoromethyl)phenyl)-N5-(3-(pyrimidin-4-yl)pyridin-2-yl)isoquinoline-1,5-diamine

Lösungsmittel

dioxane

EtOAc

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwere added
2. 2
   TemperaturThe reaction mixture was cooled
3. 3
   ExtraktionThe aqueous layer was back extracted 2× EtOAc
4. 4
   WaschenThe combined organics were washed with brine
5. 5
   Trocknendried with magnesium sulfate
6. 6
   Einengenconcentrated under vacuum
7. 7
   Sonstigepurified by column Chromatgraphy

Vorschrift

To 6-methyl-N5-(3-(pyrimidin-4-yl)pyridin-2-yl)isoquinoline-1,5-diamine (0.040 g, 0.12 mmol), charged to a 5 mL mircowave reaction vessel, 2-bromo-1-methyl-4-(trifluoromethyl)benzene (0.044 g, 0.18 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (0.016 g, 0.027 mmol), cesium carbonate (0.056 g, 0.17 mmol), and tris(dibenzylideneacetone)dipalladium (o) (0.011 g, 0.012 mmol) were added. The reagents were then suspended in dioxane (2.0 mL). The reaction mixture was stirred at 140° C. for 1 hrs. The reaction mixture was cooled and diluted with excess EtOAc, and partioned with aqueous sodium carbonate. The aqueous layer was back extracted 2× EtOAc. The combined organics were washed with brine, dried with magnesium sulfate and concentrated under vacuum. The resulting residue was loaded on to silica and purified by column Chromatgraphy. (ISCO 40.0 g, 0.5-5% MeOH in DCM, 30 min.) to give 6-methyl-N1-(2-methyl-5-(trifluoromethyl)phenyl)-N5-(3-(pyrimidin-4-yl)pyridin-2-yl)isoquinoline-1,5-diamine as a solid after treatment with diethyl ether. MS (M+H)+ 487.

Quelle