3-aMino-5,6-dichloropyrazine-2-carboxylic acid

Preparative Example 72. Preparation of Table 1 Compound No. 207; A suspension of 100 (3.6 g, 16 mmol, Aldrich) and sodium hydroxide (1.6 g, 39 mmol) in water (30 ml_) was heated at reflux for 15 min. The solution was filtered, allowed to cool to room temperature, and was acidified with 1 N hydrochloric acid. The precipitated solid 101 (1.2 g, 36percent yield) was collected by filtration, air-dried, and dried further under vacuum.A solution of 101 (1.1 g, 5.3 mmol) in concentrated sulfuric acid (9 mL) was cooled to 0 C and a 1 :1 (v/v) nitric acid-sulfuric acid mixture (680 muL) was added. The reaction mixture was stirred at room temperature for 3 hours, then poured into ice (-150 mL). The precipitated solid was collected by filtration and then dissolved in ethyl acetate. The organic solution was neutralized with saturated aqueous sodium carbonate solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give 102 (619 mg, 56% yield).Preparation of 5, 6-dichloro-3-nitropyrazinamine (II) To 450 ml concentrated sulfuric acid cooled to 10 is added 50.0 g (0.2 m) 3-amino-5, 6-dichloropyrazine carboxylic acid. To this solution cooled to 0-5, is added a cold solution of 15 ml fuming sulfuric acid in 15 ml fuming nitric acid dropwise over 15 minutes. The reaction mixture is stirred at 0-5 for 2 hours and then at ambient temperature for 2 hours. The reaction mixture is then poured onto ice and the yellow solid is collected. This solid is taken up in ethyl acetate, washed twice with saturated sodium carbonate solution and then the solution is filtered through a pad of silica gel. The resulting solution is evaporated in vacuo to afford 35 g of 5, 6-dichloro-3-nitropyrazinamine, m.p. 169-170 C.STEP A: Preparation of 5, 6-dichloro-3-nitropyrazinamine (II) To 450 ml concentrated sulfuric acid cooled to 10 is added 50.0 g (0.2 m) 3-amino-5, 6-dichloropyrazine carboxylic acid. To this solution cooled to 0-520, is added a cold solution of 15 ml fuming sulfuric acid in 15 ml fuming nitric acid dropwise over 15 minutes. The reaction mixture is stirred at 0-5 for 2 hours and then at ambient temperature for 2 hours. The reaction mixture is then poured onto ice and the yellow solid is collected. This solid is taken up in ethyl acetate, washed twice with saturated sodium carbonate solution and then the solution is filtered through a pad of silica gel. The resulting solution is evaporated in vacuo to afford 35 g of 5, 6-dichloro-3nitropyrazinamine, m.p. 169-170 C.Preparation of 5, 6-dichloro-3-nitropyrazinamine (II) To a 450 ml concentrated sulfuric acid cooled to 10 is added 50.0 g (0.2 m) 3-amino-5, 6-dichloropyrazine carboxylic acid. To this solution cooled to 0-5, is added a cold solution of 15 ml fuming sulfuric acid in 15 ml fuming nitric acid dropwise over 15 minutes. The reaction mixture is stirred at 0-5 for 2 hours and then at ambient temperature for 2 hours. The reaction mixture is the poured onto ice and the yellow solid is collected. This solid is taken up in ethyl acetate, and then washed twice with saturated sodium carbonate solution and then the solution is filtered through a pad of silica gel. The resulting solution is evaporated in vacuo to afford 35 g of 5, 6-dichloro-3-nitropyrazinamine, m.p. 169-170.Example 38 5, 6-Dichloro-3-(oxalyl-amino)-pyrazine-2-carboxylic acid, dilithium salt; To a solution of Preparative Example 72. Preparation of Table 1 Compound No. 207; A suspension of 100 (3.6 g, 16 mmol, Aldrich) and sodium hydroxide (1.6 g, 39 mmol) in water (30 ml_) was heated at reflux for 15 min. The solution was filtered, allowed to cool to room temperature, and was acidified with 1 N hydrochloric acid. The precipitated solid 101 (1.2 g, 36% yield) was collected by filtration, air-dried, and dried further under vacuum.

Molecular Weight:208.00
XLogP3:1.8
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:1
Exact Mass:206.9602317
Monoisotopic Mass:206.9602317
Topological Polar Surface Area:89.1
Heavy Atom Count:12
Complexity:192
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes