2-oxopropanal

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2-oxo-propionaldehyde (0.19 mL, 1.20 mmol) and 4-fluoro-benzene-1,2-diamine (150 mg, 1.19 mmol) in water (1.3 mL) was placed in a microwave tube and heated for 1 min at 150 W. Then the reaction mixture was diluted with water and extracted twice with AcOEt. The organic phase was washed with water, brine, dried over MgSO4, filtered and evaporated. The crude residue was purified by flash chromatography (cyclohexane/AcOEt 4:1) to yield 154 mg (0.95 mmol; 80%) of 6-fluoro-2-methyl-quinoxaline. heated for 1 min at 150 W extracted twice with AcOEt The organic phase was washed with water, brine dried over MgSO4 filtered evaporated The crude residue was purified by flash chromatography (cyclohexane/AcOEt 4:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of pyruvaldehyde (40% w/w solution in water, 6.6 mL, 7.8 g, 0.058 mol) in DMSO (100 mL) at ambient temperature was added ethyl 4-aminopiperidinecarboxylate (10 g,, 0.058 mol). After 10 min, α-(p-toluenesulfonyl)-4-fluorobenzylisonitrile (8.4 g, 0.029 mol) and K2CO3 (8.0 g, 0.058 mol) were added. After stirring for 18 h, the solution was partition between EtOAc and 3N HCl and the organic phase was washed with 3N HCl. The combined aqueous layers were neutralized with solid K2CO3 and extracted twice with EtOAc. The combined organics were washed with brine, dried (MgSO4) and concentrated in vacuo to give a brown oil which solidified upon standing. Flash chromatography eluting consecutively with 33%, 50% and 67% EtOAc in hexanes followed by trituration with ether afforded the title compound as a white solid; yield 3.5 g (23%). the solution was partition between EtOAc and 3N HCl the organic phase was washed with 3N HCl extracted twice with EtOAc The combined organics were washed with brine dried (MgSO4) concentrated in vacuo to give a brown oil which Flash chromatography eluting consecutively with 33%, 50% and 67% EtOAc in hexanes

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2-oxo-propionaldehyde (0.19 mL, 1.20 mmol) and 4-fluoro-benzene-1,2-diamine (150 mg, 1.19 mmol) in water (1.3 mL) was placed in a microwave tube and heated for 1 min. at 150 W. Then the reaction mixture was diluted with water and extracted twice with AcOEt. The organic phase was washed with water, brine, dried over MgSO4, filtered and evaporated. The crude residue was purified by flash chromatography (cyclohexane/AcOEt 4:1) to yield 154 mg (0.95 mmol, 80%) of 6-fluoro-2-methyl-quinoxaline. heated for 1 min. at 150 W extracted twice with AcOEt The organic phase was washed with water, brine dried over MgSO4 filtered evaporated The crude residue was purified by flash chromatography (cyclohexane/AcOEt 4:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of pyruvaldehyde (40% w/w solution in water, 6.6 mL, 7.8 g, 0.058 mol) in DMSO (100 mL) at ambient temperature was added ethyl 4-aminopiperidinecarboxylate (10 g, 0.058 mol). After 10 min, α-(p-toluenesulfonyl)-4-fluorobenzylisonitrile (8.4 g, 0.029 mol) and K2CO3 (8.0 g, 0.058 mol) were added. After stirring for 18 h, the solution was partition between EtOAc and 3 N HCl and the organic phase was washed with 3N HCl. The combined aqueous layers were neutralized with solid K2CO3 and extracted twice with EtOAc. The combined organics were washed with brine, dried (MgSO4) and concentrated in vacuo to give a brown oil which solidified upon standing. Flash chromatography eluting consecutively with 33%, 50% and 67% EtOAc in hexanes followed by trituration with ether afforded the title compound as a white solid; yield 3.5 g (23%). the solution was partition between EtOAc and 3 N HCl the organic phase was washed with 3N HCl extracted twice with EtOAc The combined organics were washed with brine dried (MgSO4) concentrated in vacuo to give a brown oil which Flash chromatography eluting consecutively with 33%, 50% and 67% EtOAc in hexanes

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The product from Example 61A (9.4 g, 50 mmol) in acetonitrile (100 mL) was treated with 40% aqueous pyruvic aldehyde (11.0 mL, 60 mmol) dropwise. After stirring at room temperature for 2 hours, the mixture was concentrated and the residue was suspended in IPAc (100 mL) and filtered. The filtrate was washed with 20% brine, dried with Na2SO4, filtered, and the filtrate was concentrated. The residue was purified by silica gel column chromatography eluting with heptane:EtOH:MeOH (8:2:1) to provide the title compounds. MS 224 (M+H)+; 1H NMR (400 MHz, CDCl3) δ 8.73 (s, 1H), 8.72 (s, 1H), 8.23 (d, J=2.2 Hz, 1H), 8.18 (d, J=2.1 Hz, 1H), 7.75-7.93 (m, 4H), 2.78 (s, 3H), 2.76 (s, 3H); 13C NMR (400 MHz, CDCl3) δ 154.32, 153.73, 146.34, 145.83, 142.28, 141.17, 140.45, 139.34, 133.17, 132.15, 131.15, 130.75, 130.16, 129.71, 123.66, 122.38, 22.89. the mixture was concentrated filtered The filtrate was washed with 20% brine dried with Na2SO4 filtered the filtrate was concentrated The residue was purified by silica gel column chromatography eluting with heptane:EtOH:MeOH (8:2:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The product from Example 61A (9.4 g, 50 mmol) in acetonitrile (100 mL) was treated with 40% aqueous pyruvic aldehyde (11.0 mL, 60 mmol) dropwise. After stirring at room temperature for 2 hours, the mixture was concentrated and the residue was suspended in IPAc (100 mL) and filtered. The filtrate was washed with 20% brine, dried with Na2SO4, filtered, and the filtrate was concentrated. The residue was purified by silica gel column chromatography eluting with heptane:EtOH:MeOH (8:2:1) to provide the title compounds. MS 224 (M+H)+; 1H NMR (400 MHz, CDCl3) δ 8.73 (s, 1H), 8.72 (s, 1H), 8.23 (d, J=2.2 Hz, 1H), 8.18 (d, J=2.1 Hz, 1H), 7.75-7.93 (m, 4H), 2.78 (s, 3H), 2.76 (s, 3H); 13C NMR (400 MHz, CDCl3) δ 154.32, 153.73, 146.34, 145.83, 142.28, 141.17, 140.45, 139.34, 133.17, 132.15, 131.15, 130.75, 130.16, 129.71, 123.66, 122.38, 22.89. the mixture was concentrated filtered The filtrate was washed with 20% brine dried with Na2SO4 filtered the filtrate was concentrated The residue was purified by silica gel column chromatography eluting with heptane:EtOH:MeOH (8:2:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In 50 mL of H2O is dissolved 1.77 g (0.01 mole) of 4,5,6-triamino-pyrimidine-2-one hydrochloride (19). The pH of the solution is adjusted to 5 and then, 4 mL of 40% aqueous methylglyoxal (FLUKA AG, Switzerland) is added and the solution is heated under reflux for 30 minutes. The resulting precipitate is collected and purified by recrystallization from a large amount of H2O to give 20. the solution is heated under reflux for 30 minutes The resulting precipitate is collected purified by recrystallization from a large amount of H2O

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In 50 mL of H2O is dissolved 1.77 g (0.01 mole) of 4,5,6-triamino-pyrimidine-2-one hydrochloride (19). The pH of the solution is adjusted to 5 and then, 4 mL of 40% aqueous methylglyoxal (FLUKA AG, Switzerland) is added and the solution is heated under reflux for 30 minutes. The resulting precipitate is collected and purified by recrystallization from a large amount of H2O to give 20. the solution is heated under reflux for 30 minutes The resulting precipitate is collected purified by recrystallization from a large amount of H2O