SYNTHESIS OF VARIOUS GEFITINIB INTERMEDIATE DERIVATIVE AS ANTI-CANCER DRUGS

• Main Author: Lutfi Sa'adah, Pipih
• Format: Final Project
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/75118
• Institution: Institut Teknologi Bandung

Lung cancer is among the leading causes of death, highest after breast and prostate cancer. The cause of lung cancer is a gene mutation in the signaling pathway epidermal growth factor receptor (EGFR). EGFR is a receptor tyrosine kinase group that can promote excessive cell growth, proliferation, and apoptosis. Gefitinib is a drug that is widely used for cancer, especially non-small cell lung cancer (NSCLC). However, Indonesia still needs to import raw materials from overseas in order to produce gefitinib, which has made Indonesia dependent on the supply of pharmaceutical raw materials. As a result, this research aims to produce gefitinib intermediates utilizing 3-hydroxy-4-methoxybenzoate (1) as a precursor. The three primary processes in the production of gefitinib intermediates derivatives are esterification, OH group protection, and nitration. This study has effectively 3-hydroxy-4-methoxy-2,6-dinitrobenzoate (2) with a yield of 49,8%, methyl 3-hydroxy-4- methoxybenzoate (3) with a yield of 79,6%, methyl 4-methoxy-3-(3- morpholinopropoxy)benzoate (4) with a yield of 89,0%, methyl 3-(3-chloropropoxy)-4- methoxybenzoate (5) with a yield of 71,3%, methyl 3-(benzyloxy)-4-methoxybenzoate (6) with a yield of 97,0%, 4-(3-(2-methoxy-4-nitrophenoxy)propyl)morpholine (7) with a yield of 81,0%, methyl 5-(3-chloropropoxy)-4-methoxy-2-nitrobenzoate (8) with a yield of 81,5%, and methyl 3-(benzyloxy)-4-methoxy-2-nitrobenzoate (9) with a yield of 78,3%. The reaction was followed by thin layer chromatography (TLC). Each synthesized product was characterized using 1D NMR (1H, 13C NMR), 2D NMR (HSQC and HMBC), and MS.