40381-90-6Relevant articles and documents
Preparation method of key intermediate heterocyclic compound 2, 6-dichloronicotinic acid of obrutinib
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Paragraph 0027; 0032-0034; 0040-0041; 0045-0046; 0051; ..., (2021/11/27)
The invention relates to a preparation method of key intermediate heterocyclic compound 2, 6-dichloronicotinic acid of obrutinib, which comprises the following steps: adding 2, 6-dichloropyridine into tetrahydrofuran, dropwise adding chlorosulfonyl isocyanate at 0-5 DEG C, completely reacting at room temperature, and adding reaction liquid into ice water for quenching; and extracting with an organic solvent, and concentrating an organic layer under reduced pressure to obtain 2, 6-dichloronicotinonitrile; and adding sulfuric acid and water for refluxing, cooling to room temperature after the reaction is finished, adjusting the pH value to 8-9 by using ammonia water, and filtering to obtain 2, 6-dichloronicotinamide; adding the 2, 6-dichloronicotinamide into water, using a 10% hydrochloric acid aqueous solution until the pH value is 1-2, extracting with an organic solvent, washing an organic layer with saturated sodium chloride, and concentrating the organic layer under reduced pressure to obtain a 2, 6-dichloronicotinic acid crude product; and adding an organic solvent, stirring and dissolving, adjusting the pH value to 9-10 by using alkaline water, adjusting the pH value of a water phase to 1-2 by using concentrated hydrochloric acid, and separating out a white product 2, 6-dichloronicotinic acid. The synthetic route is simple to operate and suitable for industrial production.
Stable and reusable nanoscale Fe2O3-catalyzed aerobic oxidation process for the selective synthesis of nitriles and primary amides
Murugesan, Kathiravan,Senthamarai, Thirusangumurugan,Sohail, Manzar,Sharif, Muhammad,Kalevaru, Narayana V.,Jagadeesh, Rajenahally V.
supporting information, p. 266 - 273 (2018/01/12)
The sustainable introduction of nitrogen moieties in the form of nitrile or amide groups in functionalized molecules is of fundamental interest because nitrogen-containing motifs are found in a large number of life science molecules, natural products and materials. Hence, the synthesis and functionalization of nitriles and amides from easily available starting materials using cost-effective catalysts and green reagents is highly desired. In this regard, herein we report the nanoscale iron oxide-catalyzed environmentally benign synthesis of nitriles and primary amides from aldehydes and aqueous ammonia in the presence of 1 bar O2 or air. Under mild reaction conditions, this iron-catalyzed aerobic oxidation process proceeds to synthesise functionalized and structurally diverse aromatic, aliphatic and heterocyclic nitriles. Additionally, applying this iron-based protocol, primary amides have also been prepared in a water medium.
PYRIDINES AND PYRIDINE N-OXIDES AS MODULATORS OF THROMBIN
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Page/Page column 31-32, (2010/11/28)
The present invention describes compounds of Formula I: wherein W, X, Y, Z, and Q are defined herein, or a pharmaceutically acceptable salt thereof, for the prophylaxis, or treatment of diseases and conditions related to thrombin activity in a mammal.
