1092364-38-9

Poziotinib [1. {4. [4. (3,4. Dichloro.2.monofluoroaniline) -7-methoxyquinazoline-6. Oxygen]. 1. Piperidinyl} propan-2-ene-1one (1)] is a novel oral cancer cell inhibitor developed by Seoul Medical University in South Korea in 2008. It is used for the treatment of breast and gastric cancer, and has targeted Small molecule inhibitor of tyrosine kinase. It is currently in Phase II / III clinical research and can be used alone or in combination for the treatment of gastric, non-small cell lung cancer and breast cancer. Poziotinib is resistant to erlotinib and gefitinib EGFR L858R / T790M Double mutant cells have a strong inhibitory effect.
The combined use of Poziotinib (HM781-36B) and 5-fluorouracil, platinum compound, paclitaxel or gemcitabine shows a good synergistic inhibitory effect on the overexpression of human epidermis No. 2 (HER2). A new third-generation anti-tumor cell inhibitor following the kinase inhibitor afatinib.

Poziotinib is suitable for the treatment of patients with advanced NSCLC with exon 20 mutations in EGFR. Multiple patients have proven effective. Poziotinib is also valuable for patients with advanced NSCLC who are resistant to first-generation EGFR TKI and T790M / MET negative. There are no clinical data on the treatment of patients with brain metastases by Poziotinib. One patient with advanced NSCLC with exon 20 mutation in EGFR had meningeal metastases. This patient has been taking Poziotinib for effective control for 4 months.

1429757-65-2

1620740-65-9

1092364-38-9

Bocitinib intermediate 4-(3,4-dichloro-2-fluorophenylamino)-7-methoxyquinazolin-6-ol (12 g, 34 mmol) and compound (CAS:1620740-65-9) 4-methylbenzenesulfonic acid 1-acryloylpiperidin-4-yl ester (16 g, 51 mmol) were added to K2CO3 prepared in step (1-1) ( 9.4 g, 68 mmol) and dimethylacetamide (DMAc, 300 mL) were mixed. The reaction mixture was heated to 70 °C and stirred at this temperature for 24 hours. Upon completion of the reaction, the mixture was cooled to room temperature and extracted with ethyl acetate (300 mL) followed by washing with water (300 mL). The organic layer was separated and concentrated under reduced pressure. Ethyl acetate was added to the residue to solidify it, and after filtration and drying, the target product 1-(4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxy-6-quinazolinyl)oxy)-1-piperidinyl)-2-propen-1-one was obtained (12.8 g, Yield: 77%).1H-NMR (300 MHz, DMSO-d6) δ 9.65 (bs, 1H), 8.40 (s, 1H), 7.88 (s, 1H), 7.64-7.56 (m, 2H), 7.24 (s, 1H), 6.89-6.80 (m, 1H), 6.15-6.08 (m, 1H), 5.70-5.66 (m, 1H), 4.78 (m, 1H), 3.94 (s, 3H) , 3.87 (m, 2H), 3.48 (m, 2H), 2.03 (m, 2H), 1.70 (m, 1H).