Category: 2016-99-1

Adding a certain compound to certain chemical reactions, such as: 2016-99-1, 2,6-Dibromoisonicotinic acid, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound, Application In Synthesis of 2,6-Dibromoisonicotinic acid, blongs to pyridine-derivatives compound. Application In Synthesis of 2,6-Dibromoisonicotinic acid

To a stirred solution of commercially available 2,6-dibromoisonicotinic acid (3 g, 10.7 mmol) in THF (77 ml) was added N,N-diisopropylethylamine (3.45 g, 4.66 ml, 26.7 mmol), commercially available 2-methylpropan-2-amine (956 mg, 1.37 ml, 12.8 mmol) and TBTU (4.46 g, 13.9 mmol). The reaction mixture was allowed to stir for 17h at room temperature, filtered, evaporated and purified by flash chromatography on silica gel [heptane/ ethyl acetate (0-50%)] to yield 2,6-dibromo-N-tert-butylpyridine-4-carboxamide (3.28 g, 91%) as an off-white solid, MS (ISP) m/z = 337.0 [(M+H)+], mp 148C.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,2016-99-1, 2,6-Dibromoisonicotinic acid, and friends who are interested can also refer to it.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; HOENER, Marius; WICHMANN, Juergen; (65 pag.)WO2017/9274; (2017); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

2016-99-1, In the chemical reaction process,reaction time,type of solvent,can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product.An updated downstream synthesis route of 2016-99-1 as follows.

2,2,6,6-tetramethylpiperidine (10 ml, 59.3 mmol, Acros Organics) was added to 2,6- dibromoisonicotinic acid (2004 mg, 7.13 mmol, Fluorochem) and (S)-3-ethylmorpholine hydrochloride (1300 mg, 8.57 mmol, Manchester Organics). The vial containing reaction mixture was sealed, heated to 200 C and stirred at 200 C for 16 h. The reaction mixture was partitioned between DCM (lOOmL) and water (150ml_) acidified with 2M HCI. The organic layer was separated and extracted with DCM (50 ml_). The organic layers were combined, dried over a hydrophobic frit, and concentrated under reduced pressure. The residue was purified by reverse phase HPLC with a gradient of 30-85% acetonitrile + 0.1% formic acid. Concentration in vacuo afforded (S)-2-bromo-6-(3- ethylmorpholino)isonicotinic acid (1268 mg, 4.02 mmol, 56.4% yield) as a brown solid. LCMS (System B, UV, ESI): Rt = 1.14 min, [M+H]+ 315 + 317

The chemical industry reduces the impact on the environment during synthesis 2016-99-1, I believe this compound will play a more active role in future production and life.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; BRAVI, Gianpaolo; HOBBS, Heather; INGLIS, Graham George Adam; NICOLLE, Simon; PEACE, Simon; (138 pag.)WO2019/115640; (2019); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem