The Medical Use and Application Transformation of 3-Amino-5-methylisoxazole

The medical use and application transformation of 3-amino-5-methylisoxazole

3-Amino-5-methylisoxazole is an intermediate in the production of broad-spectrum antibiotic sulfamethoxazole, white crystal. The melting point is 51.5°C and the boiling point is 235°C. Soluble in alcohol and ether, volatile with water vapor. Pharmaceutical intermediates. Used in the production of sulfa drugs, especially the anti-infective drug sulfamethoxazole. Sumophen, a broad-spectrum antibiotic, belongs to the first-class antibacterial class, white crystalline powder; odorless, slightly bitter taste; almost insoluble in water, easily soluble in dilute hydrochloric acid, sodium hydroxide solution or ammonia solution; melting point: 168 ℃-172℃. It is used for urinary tract infection, respiratory tract infection, skin purulent infection, tonsillitis; it is contraindicated for those allergic to sulfonamides and severe liver and kidney patients. The antibacterial spectrum is similar to that of SD, but the antibacterial effect is stronger. The metabolites of sulfonamides, acetylates, have low solubility and are prone to crystallization in the urethra, resulting in crystalluria, hematuria, and urinary retention. High doses should be taken together with sodium bicarbonate. Combined with synergists, its antibacterial efficacy can be significantly enhanced, which can be increased several times to dozens of times. It is clinically used for tonsillitis, acute bronchitis, lung infection, urinary tract infection, skin purulent infection, bacillary dysentery and typhoid fever, etc.
3-Amino-5-methylisoxazole, the English name is 3-Amino-5-methylisoxazole, it is a white or beige solid at normal temperature and pressure. 3-Amino-5-methylisoxazole can be used as an intermediate in organic synthesis and biochemical synthesis, and can be used for the derivatization of drug molecules and bioactive molecules. In addition, 3-amino-5-methylisoxazole is a key synthetic intermediate of the drug molecule sulfamethoxazole.

Solubility:
3-Amino-5-methylisoxazole can be dissolved in common organic solvents such as N,N-dimethylformamide, dimethyl sulfoxide, etc. It also has certain solubility in non-polar organic solvents. It should be noted that 3-amino-5-methylisoxazole is also soluble in water.

Medicinal use:
3-Amino-5-methylisoxazole is the key synthetic intermediate of the drug molecule sulfamethoxazole, which is currently the most commonly used variety in sulfa drugs. Compound sulfamethoxazole can kill many kinds of bacteria, purulent tonsil Inflammation, pharyngitis, pneumonia, bronchitis, dysentery, urinary tract infection, and many other infectious diseases can be used.

Production method:
By 5-methylisoxazole-3-formamide degradation derived. First pass quantitative chlorine into 1.02 times sodium hydroxide solution below 23°C to obtain sodium hypochlorite solution. Add 5-methylisoxazole-3-carboxamide to sodium hypochlorite at 20-25°C and react for 2 hours. The reaction liquid was adjusted to 5.6% alkali concentration with sodium hydroxide solution, and then passed through a pipeline at 176°C with an internal pressure of about 0.75 MPa at a flow rate of 1.5 L/min. The effluent was extracted with chloroform, the extracts were combined, the chloroform was recovered, and the residue was cooled to obtain 3-amino-5-methylisoxazole.

A solution of 3-amino-5-methylisoxazole (1.0 g) in THF (20 mL) and an aqueous solution of pyridine were slowly added dropwise to NaOCl solution (∼10%, 50 mL) at 0 °C, and then The reaction mixture was stirred at 0° C. for 1 hour, the precipitate formed during the reaction was filtered, and the precipitate was dried under vacuum. The phthalate was then dissolved in EtOH (50 mL) and hydrazine hydrate solution (20 mL, 98%) was added to the reaction mixture at room temperature, then the reaction mixture was stirred at 60 °C and the reaction progress was monitored by TLC. After the reaction, the reaction mixture was poured into ice water, the formed precipitate was filtered and dried under vacuum to obtain the target product molecule.

To a solution of 3-amino-5-methylisoxazole (9.8 g, 100 mmol) in dichloromethane (200 ml) was added N-chlorosuccinimide (14.6 g, 110 mmol) at 0°C mol), the time of the dropwise addition was 20 minutes, and the resulting reaction mixture was stirred overnight at room temperature. The reaction mixture was then concentrated and extracted between 1N NaOH (150 mL) and ethyl acetate (400 mL), the organic layer was separated and washed with 1N NaOH, water, brine, and the separated organic layer was dissolved in anhydrous MgSO4 The filtrate was concentrated under vacuum to give a brown solid. The resulting residue was recrystallized from chloroform/n-hexane to give the target product 3-amino-4-chloro-5-methylisoxazole as a brown solid (9.5 g, 71%).