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;,
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