SYNTHESIS OF CHLOROMETHYL PYRIDINE DERIVATIVE COMPOUNDS AS A PRECURSOR OF GERD DRUG LANSOPRAZOLE

• Main Author: Azmi Na'imah Shidiqiah, Tsabita
• Format: Final Project
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/79558
• Institution: Institut Teknologi Bandung

Gastroesophageal reflux disease (GERD) is a disease commonly diagnosed in Indonesia. This disease can be treated by Proton Pump Inhibitor (PPI) drugs, which are one of the classes of drugs with the most effective performance among other drug classes for treating GERD. Lansoprazole is included in the group of commercial PPI drugs that are often used but are currently rarely produced locally in Indonesia. In this research, the synthesis and optimization of the precursor for the GERD drug lansoprazole, namely a chloromethyl pyridine derivative compound (3) is reported. The methodology for the synthesis of chloromethyl pyridine derivative (3) includes 2 reaction stages, namely the replacement of the hydroxyl group by a chloride group on the phthalate salt precursor compound derived from methyl pyridine through a chlorination reaction using thionyl chloride; and a hydrolysis reaction to release the phthalate salt using an alkaline reagent. The phthalate salt derived from chloromethyl pyridine (2) as a reaction product in the first stage was obtained with the yield of 83.16% when the reaction was carried out with a mole ratio of phthalate salt and thionyl chloride was 1: 2. The hydrolysis was carried out on this compound with alkaline reagents. The two different bases were sodium hydroxide and potassium hydroxide. The highest yield of (3) was obtained at 42.65% using sodium hydroxide with a mole ratio of the phthalate salt (2) and sodium hydroxide was 1: 30. Increasing the scale of the reaction result in higher yield of (3) at 72.9%. The products from both stages were characterized using 1H-NMR and 13C-NMR. Based on these analysis, it can be concluded that the target compounds have been successfully synthesized.