Preparation of 2-aminoisophthalic acid dimethyl ester_Kain Industrial Additive

Background and overview^[1]

Dimethyl 2-aminoisophthalate can be used as an intermediate for pharmaceutical and chemical synthesis. If 2-aminoisophthalate dimethyl ester is inhaled, move the patient to fresh air; if skin contact occurs, take off contaminated clothing, rinse the skin thoroughly with soap and water, and seek medical attention if you feel uncomfortable; If eye contact occurs, separate eyelids, rinse with running water or saline, and seek medical attention immediately; if ingested, rinse mouth immediately, do not induce vomiting, and seek medical attention immediately.

Apply^[1]

2-Aminoisophthalic acid dimethyl ester can be used as a pharmaceutical and chemical synthesis intermediate. For example, it can be used to prepare 2-(methylsulfonylamino)isophthalic acid dimethyl ester. The specific steps are: Methylsilyldiazamethane (9.12 mL, 18.24 mmol) (2M in diethyl ether) was slowly added to 9 mL of anhydrous 2-amino-3-(methoxycarbonyl)benzoic acid (2.0 g, 10.25 mmol). A solution of tetrahydrofuran and 6 mL of methanol was then stirred at room temperature overnight. The reaction mixture was concentrated and purified by flash chromatography (1-6% methanol/CH2Cl2) to give the intermediate. Then a mixture of the above compound (1.50g, 7.17mmol), pyridine (1.74mL, 21.51mmol) and methanesulfonic anhydride (2.50g, 14.34mmol) in 60mL 1,2-dichloroethane was stirred at 80°C overnight. . The reaction mixture was concentrated and the residue was purified by flash chromatography (0-7% methanol/CHCl) to give the title compound 2-(methylsulfonylamino)isophthalic acid dimethyl ester.

Preparation ^[1]

Dimethyl 2-aminoisophthalate was prepared as follows: Trimethylsilyldiazamethane (9.12 mL, 18.24 mmol) (2M in ether) was slowly added to 2-amino-3 – (Methoxycarbonyl)benzoic acid (2.0 g, 10.25 mmol) was dissolved in anhydrous 9 mL of tetrahydrofuran and 6 mL of methanol, and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated and purified by flash chromatography (1-6% methanol/CH2Cl2) to give the title compound 2-aminoisophthalic acid dimethyl ester.

Main reference materials

[1] US20130018045. Chemical entities to be used for Wee1 inhibition for the treatment of cancer