Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 289039-83-4, name is Methyl 2-amino-5-bromo-3-iodobenzoate, A new synthetic method of this compound is introduced below., name: Methyl 2-amino-5-bromo-3-iodobenzoate
To a solution of methyl 2-amino-5-bromo-3-iodobenzoate (7.47 g, 20.99 mmol) in TEA (40 mL, 287 mmol) is added Pd(PPh3)2C12 (0.884 g, 1 .259 mmol), and copper(l) iodide (0.240 g, 1.259 mmol). The mixture is stirred under N2 for about 5 mm, and then trimethylsilylacetylene (3.83 mL, 27.3 mmol) is added. The mixture is stirred at rt for I h. The reaction is followed by LCMS (only 6% product after I h). The mixture is then transferred to a pressure tube and additional Pd(PPh3)2C12 (0.14 g, 0.199 mmol) and copper(l) iodide (0.036 g, 0.189 mmol) are added. The mixture is purged with N2 for 1 mm, and then it is heated at 60 C for 2 h (LCMS shows 54% mono-alkyne and 35% bis-alkyne). The reaction mixture is concentrated under reduced pressure. The residue is taken up in CH2CI2 and filtered through a plug of Celite. The Celite plug is washed with CH2CI2. The filtrate is washed with water (2x) and brine (lx), dried over Na2SO4, filtered and concentrated. The residue is chromatographed over silica gel (120 g ISCO column) eluting with 0-5% EtOAc/hexane gradient to yield a mixture of methyl 2-amino-5- bromo-3-((trimethylsilyl)ethynyl)benzoate and methyl 2-amino-3, 5- bis((trimethylsilyl)ethynyl)benzoate (4.2 to I ratio by I H NMR). LCMS (ES API) MH+ = 326 & 328 for Br isotopes mono-alkyne product; and LCMS (ES API) MH+ = 344 bis-alkyne product.A mixture of methyl 2-amino-5-bromo-3-((trimethylsilyl)ethynyl)benzoate (500 mg, 1 .53mmol; contaminated with 20% of methyl 2-amino-3,5-bis((trimethylsilyl)ethynyl)benzoate) and2 eq of Cul (584 mg, 3.07 mmol) in DMF (4 mL) is set under N2 and heated in a sealed tube at100 C for 80 mm. Upon cooling, the reaction mixture is diluted with Et20 and filtered through aplug of Celite. The Celite plug is washed with Et20 and EtOAc. The filtrate is concentrated underreduced pressure. The residue is chromatographed over silica gel eluting with 0-15% EtOAchexane gradient to give the title compound as a light yellow solid. LCMS (ES API) MH+ = 254 &256 for Br isotopes.
The synthetic route of 289039-83-4 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.2) LIMITED; BECHERER, J. David; CADILLA, Rodolfo; DEATON, David Norman; HAFFNER, Curt; HENKE, Brad Richard; PREUGSCHAT, Frank; SCHULTE, Christie; (69 pag.)WO2016/87975; (2016); A1;,
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