Preparation background and overview of 2,4-dichloro-3-iodopyridine
2,4-Dichloro-3-iodopyridine is a pharmaceutical intermediate, which can be obtained by iodination of 2,4-dichloropyridine or by 2,4-dihydroxy-3-iodopyridine and phosphorus oxychloride Obtained by chlorination.
Preparation of 2,4-dichloro-3-iodopyridine
Preparation Report 1 of 2,4-dichloro-3-iodopyridine,
In a nitrogen atmosphere, 2,4-dichloropyridine (5.2g, 35.137mmol) and diisopropylamine (3.911g, 38.6 lithium metaborate 51mmol) were added to dry THF (40ml) cooled at -78°C. n-Butyllithium (24.157ml, 38.651mmol, 1.6M in hexane) was added dropwise to the solution. The resulting reaction mixture was stirred at -78°C for 45 minutes, and then a solution of iodine (9.81 g, 38.651 mmol) in dry THF (20 ml) was added dropwise. The mixture was stirred at -78°C for 1 hour, allowed to warm to room temperature, diluted with EtOAc and washed with NH4Cl (aqueous saturated solution) and Na2S2O3 (aqueous saturated solution) quenching. The organic layer was separated, washed with NaHCO3 (aqueous saturated solution), dried (Na2SO4) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel; heptane/DCM (up to 20%) as eluent). The desired fractions were collected and concentrated in vacuo to yield 2,4-dichloro-3-iodopyridine (7.8 g, 81%).
Preparation report 2 of 2,4-dichloro-3-iodopyridine,
Add 2hydroxymethylphenylboronic acid, 4-dihydroxy-3-iodopyridine (49.3 g, 208 mmol), DMF (0.161 ml, 2.08 mmol) and phosphoryl chloride (252 ml, 2704 mmol). The mixture was heated to 90°C overnight. The reaction mixture was concentrated, quenched with saturated NaHCO3 aqueous solution, extracted with DCM, dried, and concentrated to obtain 2,4-dichloro-3-iodopyridine.
References
[1] [Invented in China, authorized by China] CN201580067363.X 1,2,4-triazolo[4,3-a]pyridine compound and its use as a positive allosteric modulator of mGluR2 receptor 【Public】
[2] [Invented in China] CN201310357404.1 Viral polymerase inhibitor
