Chemical Properties
White crystalline
Uses
Methyl 3-Iodo-4-methylbenzoate is used as a reagent in the synthesis of [(pyrazolo[1,5-a]pyridmidinyl)ethynyl]benzamides as selective discoidin domain receptor 1 (DDR1) inhibitors. Also used as a reagent in the preparation of orally bioavailable GZD824 targeting Breakpoint Cluster Region-Abelson (Bcr-Abl) kinase and overcoming antitumor drug resistance.
Synthesis
1. 3-iodo-4-methylbenzoic acid (28.0 g, 0.107 mol) was dissolved in methanol (300 mL) at 0 °C.
2. Concentrated sulfuric acid (30 mL) was added slowly to the above solution.
3. The reaction mixture was heated to 60 °C and kept reacting overnight.
4. When the reaction is complete, cool to room temperature and remove the solvent by distillation under reduced pressure.
5. The residue was carefully poured into ice water (200 mL) and extracted with ethyl acetate (500 mL).
6. The organic phase was washed sequentially with water (100 mL), saturated sodium bicarbonate solution (100 mL) and brine (100 mL).
7. The organic phase was dried over anhydrous magnesium sulfate, filtered and concentrated to afford the target product methyl 3-iodo-4-methylbenzoate as a brown oil (29.0 g, 98% yield).
8. The product was characterized by 1H NMR (400 MHz, CDCl3): δ8.47 (d, J=1.7 Hz, 1H), 7.90 (dd, J=7.9 Hz, 1.7 Hz, 1H), 7.29 (d, J=7.9 Hz, 1H), 3.90 (s, 3H), 2.48 (s, 3H).
References
[1] Collection of Czechoslovak Chemical Communications, 1999, vol. 64, # 4, p. 649 - 672
[2] Patent: WO2014/8197, 2014, A1. Location in patent: Page/Page column 71
[3] Patent: WO2015/95767, 2015, A1. Location in patent: Page/Page column 86
[4] Patent: EP2322176, 2011, A1. Location in patent: Page/Page column 21
[5] Patent: WO2011/57757, 2011, A1. Location in patent: Page/Page column 36-37
