Preparation of 2,4-dichloro-3-iodopyridine_Industrial additives

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