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With ammonia In water at 160℃; for 24 h; Alkaline aqueous solution
A mixture of 2-chloro-3-methylpyrazine (7 g, 54.69 mmol) and 25percent NH3.H2O (100 mL) was heated to 1600C for 24h in a sealed tube. The resulting solution was cooled to RT and extracted with EtOAc (3x200 mL). The organics were combined, dried over Na2SO4, and concentrated under vacuum to afford 2.18 g (89percent) of 3-methylpyrazin-2-amine as a yellow solid. LCMS: 110 (M+H)+.
36%
With ammonia In methanol at 150℃; for 8 h;
In an autoclave, 2-chloro-3-methyl-pyrazine (1) (10.0 g, 77.8 mmol) was dissolved in dry methanol (30 mL). Ammonia gas (60 g) was added. The mixture was heated to 150°C for 8 hours. (start pressure: 10 bar, end pressure: 90 bar). After cooling to rt, the mixture was evaporated to a brown solid, which was dissolved in IN hydrochloric acid (100 mL) and washed with dichloromethane. The aqueous layer was slowly poured on cold saturated aqueous ammonia (150 mL), then extracted with dichloromethane (3 x 100 mL). The combined organic layers were dried (Na2SO4) and evaporated. The product was extracted from the residual solid with hot acetone (200 mL). Evaporation yielded 36 percent of 3-methyl-pyrazin-2- ylamine (2) as a yellow solid
36%
Stage #1: With ammonia In methanol at 150℃; for 8 h; Stage #2: With hydrogenchloride In methanol; water at 20℃; Stage #3: With ammonia In methanol; water at 20℃;
In an autoclave, 2-chloro-3-methyl-pyrazine (1) (10.0 g, 77.8 mmol) was dissolved in dry methanol (30 mL) . Ammonia gas (60 g) was added. The mixture was heated to 15O0C for 8 hours, (start pressure: 10 bar, end pressure: 90 bar) . After cooling to rt, the mixture was evaporated to a brown solid, which was dissolved in IN hydrochloric acid (100 mL) and washed with dichloro- methane . The aqueous layer was slowly poured on cold saturated aqueous ammonia (150 mL) , then extracted with dichloromethane (3 x 100 mL) . The combined organic layers were dried (Na2SO4) and evaporated. The product was extracted from the residual solid with hot acetone (200 mL) . Evaporation yielded 36 percent of 3-methyl-pyrazin-2- ylamine (2) as a yellow solid.
2-(N,N-dibenzylamino-ethoxy)-3-methylpyrazine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With hydrogenchloride; In N-methyl-acetamide; (2S)-N-methyl-1-phenylpropan-2-amine hydrate; paraffin;
(a) 36.2 g of 2-N,N-dibenzylaminoethanol are dissolved in 375 ml of dimethylformamide and 6.6 g of a 55% strength suspension of sodium hydride in paraffin are added in portions at 0-5 C., whilst stirring. When the evolution of hydrogen has ceased, 23.1 g of 2-methyl-3-chloropyrazine, dissolved in 75 ml of dimethylformamide, are added dropwise to the reaction mixture at 0-5 C., whilst stirring. After completion of the addition, the mixture is slowly warmed to 80 C. and stirred at 80 C. for 15 hours. The reaction mixture is then cooled and poured onto 1 liter of ice water. The aqueous suspension is extracted by shaking with ether, the combined ether extracts are extracted by shaking with 2 N hydrochloric acid and the hydrochloric acid extracts are rendered alkaline with concentrated sodium hydroxide solution and extracted with ether. This ether extract is washed with water, dried over sodium sulphate and evaporated under a waterpump vacuum, giving 2-(N,N-dibenzylamino-ethoxy)-3-methylpyrazine, from which the hydrochloride is prepared by means of a solution of hydrochloric acid in ether, and is recrystallized from methanol/acetone; melting point 166-178 C.
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In tetrahydrofuran; water; toluene; at 100℃; for 15h;
A mixture of 2-chloro-3-methylpyrazine (5 g, 38.89 mmol), KOAc (7.62 g, 77.78 mmol), <strong>[721960-43-6]2-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline</strong> (11.11 g, 50.56 mmol) and Pd(dppf)Cl2(1 g, 0.1 eq) in toluene/THF/H2O (2:2:1, 70 mL) was stirred at 100 C. for 15 hr. The reaction mixture was diluted with H2O (30 mL), extracted with dichloromethane (2*30 mL). All of the organic layers were combined, washed with brine (2*20 mL), dried over anhydrous Na2SO4, filtered and concentrated. The crude mixture was purified by silica gel column chromatography (ethyl acetate:PE=1:1) to afford the desired product 11 (3 g). LCMS m/z 220 (M+H)+
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