Description
4-chloro-7-Methoxyquinoline-6-carboxaMide is a pharmaceutical intermediate compound used in the preparation of Lenvatinib, an oral multi-receptor tyrosine kinase inhibitor approved by the FDA for the treatment of radioiodine-refractory differentiated thyroid cancer (DTC), unresectable (DTC), unresectable hepatocellular carcinoma (HCC), and advanced renal cell carcinoma (RCC).
Synthesis
General procedure for the synthesis of 4-chloro-7-methoxyquinoline-6-amide from methyl 4-chloro-7-methoxyquinoline-6-carboxylate: 4.1) Ammonia (200 mL, 5.2 mol) was added to a 500 mL three-necked flask, followed by the addition of Compound IV (10 g, 39.8 mmol) obtained from Step 3.3) to obtain Mixture H; 4.2) Mixture H was was reacted at 60 °C for 4 h. After completion of the reaction, the mixture was cooled to room temperature to obtain mixture I. 4.3) Three extractions were performed by adding dichloromethane to mixture I, resulting in a light yellow solid compound V in 85.17% yield.
References
[1] Journal of Medicinal Chemistry, 2008, vol. 51, # 6, p. 1668 - 1680
[2] Patent: CN107629001, 2018, A. Location in patent: Paragraph 0112; 0128-0131; 0164-0167; 0199-0202; 0235-0238
[3] Patent: EP1724268, 2006, A1. Location in patent: Page/Page column 48
[4] Journal of Medicinal Chemistry, 2008, vol. 51, # 6, p. 1649 - 1667
