Reaktion #1756096

Reaktionsgleichung

Lithium bis (trimethylsilyl)amide

6-Methyl-N1-(3-(trifluoromethyl)phenyl)isoquinoline-1,5-diamine

4-(2-chloropyridin-3-yl) pyrimidine

N,N-dimethylaminobiphenyl

→

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

Ausbeute 56.4%

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeall placed in a sealed tube
2. 2
   Sonstigewas bubbled into the reaction mixture for 5 min
3. 3
   SonstigeThe tube was capped
4. 4
   Temperaturto cool to room temperature
5. 5
   Sonstigequenched with methanol
6. 6
   SonstigeThe volatiles were removed in vacuo
7. 7
   Waschenwashed (2×) with an aqueous saturated solution of sodium bicarbonate
8. 8
   TrocknenThe organic layer was then dried with sodium sulfate
9. 9
   Sonstigethe purified by column chromatography on silica gel using a gradient of 20 to 60% EtOAc in hexanes

Vorschrift

6-Methyl-N1-(3-(trifluoromethyl)phenyl)isoquinoline-1,5-diamine (0.100 g, 0.30 mmol), 4-(2-chloropyridin-3-yl) pyrimidine (0.057 g, 0.30 mmol), dicyclohexylphosphino)-N,N-dimethylaminobiphenyl (0.0094 g, 0.024 mmol), and Pd2(dba)3 (0.010 g, 0.012 mmol) were all placed in a sealed tube containing 5 mL of anhydrous THF. Lithium bis (trimethylsilyl)amide (1.0 M in THF, 0.90 mL, 0.90 mmol) was then added to the mixture and nitrogen was bubbled into the reaction mixture for 5 min. The tube was capped and the reaction heated to 70° C. overnight. The reaction was allowed to cool to room temperature and quenched with methanol. The volatiles were removed in vacuo. The residue was taken up in ethyl acetate and washed (2×) with an aqueous saturated solution of sodium bicarbonate, then with water and then brine. The organic layer was then dried with sodium sulfate and the purified by column chromatography on silica gel using a gradient of 20 to 60% EtOAc in hexanes to give 6-methyl-N5-(3-(pyrimidin-4-yl)pyridin-2-yl)-N1-(3-(trifluoromethyl)phenyl)isoquinoline-1,5-diamine as a yellow solid (80 mg, 56%). MS (M+H)+ 473.

Quelle