Synthesis and in vitro evaluation of antimycobacterial and cytotoxic activity of new α,β-unsaturated amide, oxazoline and oxazole derivatives from -serine

Development of a Robust and Scalable Process for the Large-Scale Preparation of Vadadustat

“…Although amidation reactions appear common in pharmaceutical synthesis, we have encountered several issues that needed to be addressed. At first, CDI, 1-ethyl-3-(3-dimethylaminopropyl)­carbodiimide (EDCI), , and N , N ′-dicyclohexylcarbodiimide (DCC) were screened as carboxyl activating agents for the coupling of 13 and methyl glycinate. While EDCI and DCC failed to provide satisfying results, CDI was preferred with an assay yield of about 92% of product 14 (vs 30% by DCC and 1.8% by EDCI).…”

“…The crude solid product was collected by filtration and recrystallized from isopropyl alcohol (14 L), filtered, and dried under vacuum at 60 °C to yield the titled compound as a yellow solid (0.98 kg, 68% yield). HPLC purity: 96.8%, 1 Preparation of 5-(3-Chlorophenyl)-3-methoxypicolinic Acid (13). In a 30 L reaction kettle, 3-chloro-5-(3chlorophenyl)picolinonitrile 10 (0.85 kg, 3.41 mol), sodium methylate solution (30 wt % in methanol, 1.23 kg, 6.83 mol), and methanol (8.5 L) were placed, and then, the resulting mixture was heated to reflux and stirred for 6 h under a nitrogen atmosphere.…”

“…HPLC purity: 98.0%, 1 H NMR (400 MHz, DMSO-d 6 ): δ 8.49 (s, 1H), 7.99−7.73 (m, 3H), 7.54 (s, 2H), 3.97 (s, 3H). 13 14). A mixture of 5-(3chlorophenyl)-3-methoxypicolinic acid 13 (water content 3.22%, 0.75 kg, 2.84 mol), 1,1′-carbonyldiimidazole (CDI, 0.77 kg, 4.75 mol), and DCM (3.75 L) was stirred at room temperature.…”

“…HPLC purity: 97.1%, 1 H NMR (400 MHz, DMSO-d 6 ): δ 8.79 (t, J = 5.9 Hz, 1H), 8.52 (s, 1H), 7.96 (s, 1H), 7.86 (s, 1H), 7.82 (d, J = 7.0 Hz, 1H), 7.61−7.51 (m, 2H), 4.03 (d, J = 6.0 Hz, 2H), 3.96 (s, 3H), 3.67 (s, 3H). 13 solution was stirred for about 6 h at 85 °C. After the complete conversion of the starting material, the reaction mixture was cooled to room temperature and then added dropwise to the hydrochloric acid solution (0.44 kg, 4.22 mol, diluted with 7.7 L of H 2 O) over 1 h and stirred at room temperature for 2 h. The crude solid was isolated by filtration and was added in a mixed solution of acetone−H 2 O (9.1 L; 10:3, vol/vol), and then, NaOH (0.17 kg, 4.25 mol) was added.…”

Synthesis, Characterization and Cytotoxicity Evaluation of New Diphenyl Sulfone Derivatives

“…In addition, the 1,3-oxazole pharmacophore is present in the structures of numerous biologically active natural products, including those used as antibiotics and antiproliferatives [16][17][18][19][20]. Also, 1,3-oxazoles are substructures in many synthetic bioactive substances with a wide spectrum of pharmacological properties, like anticancer, anti-inflammatory, analgesic, antibacterial, antifungal, antiviral, antidiabetic, antitubercular, antiparasitic, anti-obesity, cytotoxic and antioxidant actions [21][22][23][24][25][26][27][28][29][30]. Besides, the esters of N-acyl-α-amino acids were reported to have monoamine oxidase (MAO) inhibitory, antibacterial, antitumor, anti-depressant and antileishmanial activities [31][32][33][34][35][36].…”