3-oxo-3-piperidin-1-ylpropanenitrile

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 20 ml vial 4-[[7-(2,2-dimethylpropanoyl)-5-(2-trimethylsilylethoxymethyl)-pyrrolo[2,3-b]pyrazin-2-yl]amino]benzaldehyde (35 mg, 0.0800 mmol), 3-oxo-3-(1-piperidyl)propanenitrile (18.01 mg, 0.1200 mmol), piperdine (0.02 ml, 0.15 mmol) and 3-oxo-3-(1-piperidyl)propanenitrile (18.01 mg, 0.12 mmol), were taken in methanol (5 ml). To this reaction mixture, piperdine (0.02 ml, 0.15 mmol) was added drop wise at RT. After completion of the addition, the reaction mixture was stirred for 5 hrs. Ethanol was evaporated, the residue was loaded on silica gel column and elution with CH2Cl2 to MeOH 0-2, 3% yielded 28 mg of 3-[4-[[7-(2,2-dimethylpropanoyl)-5-(2-trimethylsilylethoxymethyl)pyrrolo[2,3-b]pyrazin-2-yl]amino]phenyl]-2-(piperidine-1-carbonyl)prop-2-enenitrile. After completion of the addition Ethanol was evaporated the residue was loaded on silica gel column and elution with CH2Cl2 to MeOH 0-2, 3%

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 20 ml vial 4-[[7-(2,2-dimethylpropanoyl)-5-(2-trimethylsilylethoxymethyl)-pyrrolo[2,3-b]pyrazin-2-yl]amino]benzaldehyde (35 mg, 0.0800 mmol), 3-oxo-3-(1-piperidyl)propanenitrile (18.01 mg, 0.1200 mmol), piperdine (0.02 ml, 0.15 mmol) and 3-oxo-3-(1-piperidyl)propanenitrile (18.01 mg, 0.12 mmol), were taken in methanol (5 ml). To this reaction mixture, piperdine (0.02 ml, 0.15 mmol) was added drop wise at RT. After completion of the addition, the reaction mixture was stirred for 5 hrs. Ethanol was evaporated, the residue was loaded on silica gel column and elution with CH2Cl2 to MeOH 0-2, 3% yielded 28 mg of 3-[4-[[7-(2,2-dimethylpropanoyl)-5-(2-trimethylsilylethoxymethyl)pyrrolo[2,3-b]pyrazin-2-yl]amino]phenyl]-2-(piperidine-1-carbonyl)prop-2-enenitrile. After completion of the addition Ethanol was evaporated the residue was loaded on silica gel column and elution with CH2Cl2 to MeOH 0-2, 3%

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl thiosalicylate (1.7 g, 10.1 mM) and 1-cyanoacetylpiperidine (2.0 g, 13.1 mM) were dissolved in toluene (5 ml), and triethylamine (2 ml, 14.4 mM) was added to the solution. After heating for 30 hours under reflux, the reaction solution was concentrated to give crude crystals. The crude crystals were recrystallized from ethanol to give the title compound as needles (730 mg, 25%). After heating for 30 hours under reflux the reaction solution was concentrated to give crude crystals The crude crystals were recrystallized from ethanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The compound was synthesized from 1-cyanoacetylpiperidine (1.52 g, 10 mmol), bromoethane (3.73 mL, 50 mmol) and 1.6M n-butyllithium in hexane (13.75 mL, 22 mmol) in 40 mL of THF according to the method described in Example 393A to give 0.92 g. MS (ESI(+)) m/e 209 (M+H)+; 226 (M+NH4)+; 1H NMR (300 MHz, DMSO-d6) δ 3.44-3.67 (m, 4H), 2.00-2.10 (m, 2H), 1.79-1.86 (m, 2H), 1.43-1.70 (m, 6H), 1.03-1.07 (m, 6H). to give 0.92 g

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 20 ml vial 4-[[7-(2,2-dimethylpropanoyl)-5-(2-trimethylsilylethoxymethyl)-pyrrolo[2,3-b]pyrazin-2-yl]amino]benzaldehyde (35 mg, 0.0800 mmol), 3-oxo-3-(1-piperidyl)propanenitrile (18.01 mg, 0.1200 mmol), piperdine (0.02 ml, 0.15 mmol) and 3-oxo-3-(1-piperidyl)propanenitrile (18.01 mg, 0.12 mmol), were taken in methanol (5 ml). To this reaction mixture, piperdine (0.02 ml, 0.15 mmol) was added drop wise at RT. After completion of the addition, the reaction mixture was stirred for 5 hrs. Ethanol was evaporated, the residue was loaded on silica gel column and elution with CH2Cl2 to MeOH 0-2, 3% yielded 28 mg of 3-[4-[[7-(2,2-dimethylpropanoyl)-5-(2-trimethylsilylethoxymethyl)pyrrolo[2,3-b]pyrazin-2-yl]amino]phenyl]-2-(piperidine-1-carbonyl)prop-2-enenitrile. After completion of the addition Ethanol was evaporated the residue was loaded on silica gel column and elution with CH2Cl2 to MeOH 0-2, 3%