3-Methyl-quinoxaline-2-carboxylic Acid

Yellow Solid

3-Methyl-quinoxaline-2-carboxylic acid methyl ester (0.20 g, 0.99 mmol) was dissolved in methanol (8 mL) and 2 N sodium hydroxide (2 mL). The mixture was stirred for 30 minutes, then concentrated to about of its volume, acidified with 1 N hydrochloric acid and extracted with ethyl acetate. The combined extracts were washed with water and brine, dried over magnesium sulfate and concentrated to a solid which was dried on high vacuum (0.16 g, 87percent).Methyl 3-methylquinoxaline-2-carboxylate (101 g, 0.5 mol, prepared in Example 3) was dissolved in 3 L of ethanol.300 ml of 6N aqueous sodium hydroxide solution was added and the mixture was heated to reflux overnight.When TLC shows that the reaction has been completed.The solvent was evaporated, the reaction solid was dissolved in 1 liter of water, and the mixture was adjusted to pH 2 with 1N hydrochloric acid to precipitate a large solid, which was filtered to give a pale yellow solid.The solid was dissolved in 2000 ml of 1N sodium hydroxide, and the pH was adjusted to 2 with 1N hydrochloric acid to precipitate a large amount of solid and filtered to obtain a white pure product.64.4 g of product (yield 68percent).3-Methyl-2-quinoxalinecarboxylic acid, 2-(3-carboxypropionyl-oxy)ethyl ester, 1, 4-dioxide Sodium Salt A suspension of 728 mg. of 3-methyl-2-quinoxalinecarboxylic acid, 2-(3-carboxypropionyloxy)ethyl ester, 1, 4-dioxide in 50 ml. of water is treated with one drop of phenolphthalein and then neutralized with 1N sodium hydroxide solution. The hazy solution is subsequently filtered and evaporated to dryness under reduced pressure, 665 mg., m.p. 148 C. In a similar manner, the corresponding acids of Example XXXI are converted to their pharmaceutically acceptable basic salts.(1) 0.38 g of MQCA, 0.20 g of aminobutyric acid and a small amount of DMAP were added to 20 mL of dry DMF;(2) Under the condition of 0 C, 0.8 g of DCC was slowly added dropwise to the mixture of 5 mL of dry DMF. After the dropwise addition, the temperature was gradually raised to room temperature and the reaction was continued for 40 h.(3) the solvent is distilled off and purified by column chromatography to obtain the condensate of MQCA and aminobutyric acid, which is the product of formula (1).The solid (0.10 g, 0.53 mmol) was slurried in dichloromethane and oxalyl chloride (56 muL, 0.64 mmol) was added at 0 C. The mixture was warmed to room temperature and stirred for 1 hour, then concentrated to a tan solid (62 mg, 57%).3-Methyl-quinoxaline-2-carboxylic acid methyl ester (0.20 g, 0.99 mmol) was dissolved in methanol (8 mL) and 2 N sodium hydroxide (2 mL). The mixture was stirred for 30 minutes, then concentrated to about of its volume, acidified with 1 N hydrochloric acid and extracted with ethyl acetate. The combined extracts were washed with water and brine, dried over magnesium sulfate and concentrated to a solid which was dried on high vacuum (0.16 g, 87%).Methyl 3-methylquinoxaline-2-carboxylate (101 g, 0.5 mol, prepared in Example 3) was dissolved in 3 L of ethanol.300 ml of 6N aqueous sodium hydroxide solution was added and the mixture was heated to reflux overnight.When TLC shows that the reaction has been completed.The solvent was evaporated, the reaction solid was dissolved in 1 liter of water, and the mixture was adjusted to pH 2 with 1N hydrochloric acid to precipitate a large solid, which was filtered to give a pale yellow solid.The solid was dissolved in 2000 ml of 1N sodium hydroxide, and the pH was adjusted to 2 with 1N hydrochloric acid to precipitate a large amount of solid and filtered to obtain a white pure product.64.4 g of product (yield 68%).

A Carbadox and Olaquindox metabolite.

Molecular Weight:188.18
XLogP3:1.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:188.058577502
Monoisotopic Mass:188.058577502
Topological Polar Surface Area:63.1
Heavy Atom Count:14
Complexity:232
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes