2-Amino-3-cyanothiophene

Synthesis

2-AMINO-3-CYANOTHIOPHENE is a pharmaceutical intermediate that can be prepared in one step from 1,4-dithiane-2,5-diol and malononitrile. It has been reported in the literature as a potential candidate for preparing HPK1 inhibitors.

The starting material 1,4-dithiaran-2,5-diol (100 g, 0.66 mol, 1.0 eq) was dissolved in methanol (500 mL), followed by the addition of malononitrile (86.86 g, 1.32 mol, 2.0 eq) and triethylamine (20 mL). The reaction was carried out at 70 °C for 30 minutes. The reaction was confirmed to be complete by TLC. The reaction solution was concentrated, and the crude product was purified by silica gel column chromatography (PE:EA = 4:1) to obtain a yellow solid product (80 g, yield: 98%).

Uses

2-Aminothiophene-3-carboxynitrile is a pharmaceutical intermediate. Due to its important role in immunity, HPK1 inhibitors play an important role in malignant solid tumors or hematological malignancies (such as acute myeloid leukemia, bladder epithelial carcinoma, breast cancer, colon cancer, lung cancer, pancreatic cancer, melanoma), autoimmune diseases (such as systemic lupus erythematosus, psoriatic arthritis), and inflammatory responses.

Chemical Properties

white to light yellow crystal powder