3-AMINO-6-IODOPYRAZINE-2-CARBOXYLICACIDMETHYLESTER

1.5 equivalents of N-iodosuccinimide are added at room temperature to 5 g (32.7 mmol) of a methyl 3-aminopyrazine-2-carboxylate solution in 25 ml of dimethylformamide. The reaction medium is heated at 65°C for 1 hour, added together with 0.5 equivalents of N-iodosuccinimide and maintained at 65°C for 24 hours. After returning to room temperature, the solvent is evaporated and then the product is extracted several times with dichloromethane. The organic phases are combined, washed with 10percent sodium bisulfite solution, dried on magnesium sulfate and concentrated to yield 8 g (88percent) of methyl 3-amino-6-iodopyrazine-2-carboxylate in the form of a yellow solid.LCMS (EI, m/z): (M+l) 2801H NMR: 6H ppm (400 MHz, DMSO): 8.50 (1H, s, CHExample 3a 1.5 equivalents of N-iodosuccinimide are added at room temperature to 5 g (32.7 mmol) of a methyl 3-aminopyrazine-2-carboxylate solution in 25 ml of dimethylformamide. The reaction medium is heated at 65°C for 1 hour, added together with 0.5 equivalents of N-iodosuccinimide and maintained at 65°C for 24 hours. After returning to room temperature, the solvent is evaporated and then the product is extracted several times with dichloromethane. The organic phases are combined, washed with 10percent sodium bisulfite solution, dried on magnesium sulfate and concentrated to yield 8 g (88percent) of methyl 3-amino-6-iodopyrazine-2-carboxylate in the form of a yellow solid. LCMS (EI, m/z): (M+1) 280 Example 3a: methyl 3-amino-6-iodopyrazine-2-carboxylate 1.5 equivalents of N-iodosuccinimide are added at room temperature to 5 g (32.7 mmol) of a methyl 3-aminopyrazine-2-carboxylate solution in 25 ml of dimethylformamide. The reaction medium is heated at 65 °C for 1 hour, added together with 0.5 equivalents of N-iodosuccinimide and maintained at 65°C for 24 hours. After returning to room temperature, the solvent is evaporated and then the product is extracted several times with dichloromethane. The organic phases are combined, washed with 10percent sodium bisulfite solution, dried on magnesium sulfate and concentrated to yield 8 g (88percent) of methyl 3-amino-6-iodopyrazine-2-carboxylate in the form of a yellow solid. LCMS (EI, m/z): (M+l) 280 1H NMR: δΗ ppm (400 MHz, DMSO): 8.50 (1H, s, CHExample 3a: methyl 3-amino-6-iodopyrazine-2-carboxylate 1.5 equivalents of N-iodosuccinimide are added at room temperature to 5 g (32.7 mmol) of a methyl 3-aminopyrazine-2-carboxylate solution in 25 ml of dimethylformamide. The reaction medium is heated at 65 °C for 1 hour, added together with 0.5 equivalents of N-iodosuccinimide and maintained at 65°C for 24 hours. After returning to room temperature, the solvent is evaporated and then the product is extracted several times with dichloromethane. The organic phases are combined, washed with 10percent sodium bisulfite solution, dried on magnesium sulfate and concentrated to yield 8 g (88percent>) of methyl 3-amino-6-iodopyrazine-2-carboxylate in the form of a yellow solid. LCMS (EI, m/z): (M+l) 280 1H NMR: δΗ ppm (400 MHz, DMSO): 8.50 (1H, s, CH1.5 equivalents of N-iodosuccinimide are added at room temperature to 5 g (32.7 mmol) of a methyl 3-aminopyrazine-2-carboxylate solution in 25 ml of dimethylformamide. The reaction medium is heated at 65°C for 1 hour, added together with 0.5 equivalents of N-iodosuccinimide and maintained at 65°C for 24 hours. After returning to room temperature, the solvent is evaporated and then the product is extracted several times with dichloromethane. The organic phases are combined, washed with 10percent sodium bisulfite solution, dried on magnesium sulfate and concentrated to yield 8 g (88percent) of methyl 3-amino-6-iodopyrazine-2-carboxylate in the form of a yellow solid. LCMS (EI, m/z): (M+1) 280 Step 1: Synthesis of 3-amino-6-iodo-pyrazine-2-carboxylic acid methyl ester.[0295] Methyl 3-amino-2-pyrazinecarboxylate (10 g, 65.3 mmol) and N-iodosuccinimide(24 g, 106.7 mmol) were dissolved in anhydrous DMF (150 mL) and the mixture wasstirred at 70 °C for 15 hours under a nitrogen atmosphere. The mixture was then cooled toroom temperature and a saturated aqueous solution of sodium thiosulfate (400 mL) wasadded. The suspension was sonicated for 15 minutes, concentrated under vacuum anddispersed in water. The crude product was filtered off and washed with cold ethanol. Theresidue was crystallized from ethanol, using decolorizing charcoal to afford 3-amino-6-iodo-pyrazine-2-carboxylic acid methyl ester (11.2 g, 61 percent yield) as orange needles. 1H-NMR (d6-DMSO) 8.57 [1H] s, 7.59 [2H] s, br, 3.93 [3H] s. MS: m/z 280 [MH+].Tetrakis(triphenylphosphine)palladium(0) (176 mg, 0.152 mmol) was added to a solution of Aqueous LiOH solution (2.0 M, 0.72 ml, 1.4 mmol) was added dropwise to a suspension of

Molecular Weight:279.04
XLogP3:0.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:2
Exact Mass:278.95047
Monoisotopic Mass:278.95047
Topological Polar Surface Area:78.1
Heavy Atom Count:12
Complexity:178
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes