Dimethylformamide → 3-amino-6-(3-aminophenyl)-N-methylpyrazine-2-carboxamide

Temperature

87.5 °C

To a solution of 3-amino-6-bromo-N-methyl-2-pyrazinecarboxamide (1.23 g, 5.30 mmol) in N,N-dimethylformamide (30 mmol) were added [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with dichloromethane (1:1, 433 mg, 0.53 mmol), 3-aminophenylboronic acid (1.15 g, 7.41 mmol), and triethylamine (1.07 g, 10.6mmol). The solution was degassed with nitrogen 3-5 min. The reaction was heated at 85-90° C. for 15 h with stirring. The reaction was allowed to cool to room temperature and diluted with ethyl acetate (400 mL). The organic layer was washed with saturated aqueous sodium bicarbonate (50 mL), saturated aqueous sodium chloride (50 mL), dried over magnesium sulfate, filtered, and concentrated to give crude product. To the crude product was added 4.0 N hydrochloric acid (1,4-dioxane solution, 30 mL). The resulting solid was filtered and washed with diethyl ether/methanol (4:1). The solid was dissolved in methanol and neutralized with sufficient AG 1-X8 Resin (hydroxide form) that the pH of the solution became basic. The mixture was filtered, and the filtrate was concentrated on a rotary evaporator at reduced pressure to afford 3-Amino-6-(3-aminophenyl)-N-methylpyrazine-2-carboxamide (0.70 g, 54% yield) as dark green solid. 1H NMR (400 MHz, d6-DMSO): 8.70(br s, 1H), 8.62 (s, 1H), 7.60 (br s, 2H), 7.25 (m, 2H), 7.10 (t,. 1H), 6.15 (d, 1H), 5.06 (s, 2H), 2.8 (br s, 3H); MS (EID for C12H13N5O: 244 ).

1. customThe solution was degassed with nitrogen 3-5 min
2. temperatureto cool to room temperature
3. additiondiluted with ethyl acetate (400 mL)
4. washThe organic layer was washed with saturated aqueous sodium bicarbonate (50 mL), saturated aqueous sodium chloride (50 mL)
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customto give crude product
9. filtrationThe resulting solid was filtered
10. washwashed with diethyl ether/methanol (4:1)
11. dissolutionThe solid was dissolved in methanol and neutralized with sufficient AG 1-X8 Resin (hydroxide form) that the pH of the solution
12. filtrationThe mixture was filtered
13. concentrationthe filtrate was concentrated on a rotary evaporator at reduced pressure

ORD record

ord-b9669ddc38484357a0d6dafadae69877

Source dataset

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07704995B2