5-Chloro-2-pyrazinecarboxylic acid

5- [2 (R)- (3-CHLORO-4-METHANESULFONYL-PHENYL)-3-CYCLOPENTYL-PROPIONYLAMINO]- PYRAZINE-2-CARBOXYLIC acid HYDROXYAMIDE [000197] A solution of methyl 5-chloropyrazine-2-carboxylate (30.00 g, 0.17 mol) in tetrahydrofuran (87 mL) was treated with a solution of potassium carbonate (72.08 g, 0.52 mol) in water (261 mL). The resulting reaction mixture stirred at 25°C for 42 h. The reaction mixture was then acidified to a pH of about 2 with concentrated hydrochloric acid, diluted with a saturated aqueous sodium chloride solution (300 mL), and was continuously extracted with ethyl acetate (4L total) until no product was present in the aqueous layer. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo to afford 5-chloro-pyrazine-2-carboxylic acid (26.54 g, 96percent) as an off-white solid: mp 150-151°C ; EI-HRMS m/e calcd for CSH3CIN202 (M 157.9883, found 157.9877.Dissolve 5-chloro-pyrazine-2-carboxylic acid methyl ester (10.0 g, 57.9 mmol) in THF (65 mL) and MeOH (65 mL). Cool the solution to 0 Preparation of 5-Chloropyrazine-2-carboxylic acid To a flask fitted with overhead stirrer, condenser, thermometer and nitrogen line was added methyl 5-chloropyrazine-2-carboxylate (1.0 eq) and tetrahydrofuran (4.92 vols) under a nitrogen atmosphere. The reaction mixture was agitated until all the solid had dissolved, then filtered into a second flask. Water (8.65 vols) was added to the reaction mixture and the mixture agitated for approximately 15 minutes. Potassium carbonate (2.1 eq) was added to the reaction mixture and the mixture agitated for 16 hours at 20-25° C. Then 32percent w/w hydrochloric acid (3.76 eq) was added over 3 hours in small portions, keeping the reaction temperature 20-25° C., to a pH end point of pH2.2. The resultant slurry was heated to approximately 35-40° C. and then distilled under vacuum at this temperature distilling approximately 5.3 vols, to a final volume of approximately 9.3 vols. The mixture was then cooled to 20-25° C. over at least 2 hours, agitated for 10 hours at this temperature and then filtered. The solid was washed with water (2.8 vols), and the wet product produced dried at 35° C. in a vacuum oven. The desired product was obtained as a solid (corrected yield 91percent) Example 35-Chloropyrazine-2-carboxylic acidFehler. Es ist nicht moglich, durch die Bearbeitung von Feldfunktionen Objekte zu erstellen. Methyl 5-chloropyrazine-2-carboxylate (CAS [33332-25-1], 1 g, 5.79 mmol) was dissolved in a mixture of THF (50 ml) and water (50 ml). Lithium hydroxide monohydrate (243 mg, 5.79 mmol) was added and the reaction mixture was stirred at RT overnight. The pH was adjusted to 1 with 1M HC1 and the product was extracted with three portions of EtOAc. The combined organic layers were dried over NaA solution ofmethyl 5-chloropyrazine-2-carboxylate (345 mg, 2.0 mmol) inTHF (10 mL) was treated with a solution of potassium carbonate(552 mg, 4.0 mmol) in water (5 mL). The resulting reaction mixturewas stirred at 25 C for 1 day. Extra THF was removed in vacuo. Thereaction mixture was then acidified to a pH of about 2 with concentratedHCl. Compound 10 (216 mg, 68percent) was obtained as abrown solid by filtration. 1H NMR (300 MHz, CDCl3) d: 8.97 (s, 1H), 8.19 (s, 1H).Step 1: Preparation of 5-chloropyrazine-2-carboxylic acid [0170] To a solution 5-hydroxypyrazine-2-carboxylic acid (10 g, 71.42 mmol) in thionyl chloride (100 mL) was added N, N- dimethyl formamide (1 mL) and the reaction mixture was stirred at 80 °C for 16 h. Thionyl chloride was distilled off, the residue was diluted with ice water and extracted ethyl acetate (600 mL x 3). The combined organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude was triturated with diethyl ether to afford the title compound 5-chloropyrazine-2-carboxylic acid (10.53 g, 93percent yield) as a brown solid. Calculated M+H: 158.99; Found M+H: 159.0.Intermediate 44; 5-Chloropyrazine-2-carboxylic acid; 5-Hydroxypyrazine-2-carboxylic acid (1.0 g, 0.007 mol) was taken in thionyl chloride (10 mL), to this solution dimethylformamide (0.1 mL) was added which was heated to reflux for 16 h. After this period, excess thionyl chloride was distilled off to get crude compound, which was added to ice (20 g) and extracted with ethyl acetate (2 x 70 mL). The organic layers were combined and dried over anhydrous sodium sulphate and concentrated under reduced pressure to obtain brown solid which was triturated with diethyl ether (30 mL) to afford 600 mg (75percent) of 5-chloropyrazine-2-carboxylic acid.Step D:

Molecular Weight:158.54
XLogP3:0.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:157.9883050
Monoisotopic Mass:157.9883050
Topological Polar Surface Area:63.1
Heavy Atom Count:10
Complexity:142
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes