反応 #168265

反応方程式

2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl

DMA

(R)-6-chloro-N-(1-cyclobutylethyl)-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridin-4-amine

DMA

→

(R)-4-((1-cyclobutylethyl)amino)-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile

反応条件

後処理

1. 1
   その他was evacuated
2. 2
   workup.ADDITIONrefilled with Ar (3×)
3. 3
   その他The mixture was degassed with Ar for 15 minutes
4. 4
   workup.ADDITIONthe catalyst solution was added to the mixture
5. 5
   温度The mixture was cooled to room temperature
6. 6
   濃縮concentrated
7. 7
   workup.DISSOLUTIONThe residue was dissolved in DCM
8. 8
   その他purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient)

実験手順

A vial containing 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (67.6 mg, 0.142 mmol) and allylpalladium(II) chloride dimer (26 mg, 0.071 mmol) in DMA (400 ul) was evacuated and refilled with Ar (3×). The resulting solution was warmed to 70° C. for 20 minutes. In a separate vial was added zinc cyanide (92 mg, 0.78 mmol), (R)-6-chloro-N-(1-cyclobutylethyl)-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridin-4-amine (290 mg, 0.71 mmol) and DMA (500 uL). The mixture was degassed with Ar for 15 minutes, and the catalyst solution was added to the mixture. The resulting mixture was stirred at 120° C. overnight. The mixture was cooled to room temperature and concentrated. The residue was dissolved in DCM purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient) to give (R)-4-((1-cyclobutylethyl)amino)-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd for C21H20F3N5 [M+H]+ 400. found 400.

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