Kilogram-Scale Synthesis of a Highly Selective α₁-Adrenoceptor Antagonist (DL-028A)

Abstract

This work presents an improved eight-step process, leading to kilogram quantities of high-quality DL-028A, an antihypertensive agent. The improvements include reducing the levels of toxic reagents and the removal of dangerous processes and waste gas treatment. Moreover, specification and impurity profiles were determined.

2-((3,5-Dinitrobenzyl)thio)quinazolinones: Potent Antimycobacterial Agents Activated by Deazaflavin (F420)-Dependent Nitroreductase (Ddn)

“…The introduction of a nitro group in position 6 of 3-fluorobenzoic acid using fuming nitric acid led to intermediate 58 , which was converted into an amide. After nucleophilic aromatic substitution of amide 59 with a secondary amine, Pd/C-mediated hydrogenation afforded the desired substituted anthranilic amide, which condensed with CS 2 under basic conditions to yield 6-substituted thioquinazolinone intermediates ( 62a – d ). Subsequently, the desired compounds ( 63a – d ) were achieved through S-alkylation of 62a – d with 13a .…”

“…13 C NMR (101 MHz, DMSO- d 6 ) δ ppm 41.9 (2C, N­(CH 3 ) 2 ), 113.7 (1C, Ph), 114.7 (1C, Ph), 117.6 (1C, Ph), 120.1 (1C, Ph), 141.6 (1C, Ph), 142.3 (1C, Ph), 171.5 (1C, CO). According to a literature report, KOH (0.24 g, 4.3 mmol) was suspended in EtOH (10 mL) and the suspension was stirred at room temperature for 0.5 h to dissolve the KOH. Then, CS 2 (0.26 mL, 4.3 mmol) was added to the stirred solution and the resulting mixture was stirred for another 0.5 h to produce a yellow suspension.…”

Synthesis and Antitumor Activities of Novel 1,2,3-Triazolo[4,5-d]pyrimidine Derivatives

“…通过文献调研 [6,16,17] , 氰基乙酰胺和 5-(氯甲基)-1H- . 从活性数据来看(表 1), 大部分的化合物对所测 5 种 人类癌细胞均有明显的抑制活性, 且伴随着取代基的不 同而改变; 化合物 11l (8.21 μmol/L)、11m (5.58 μmol/L) 和 11b (9.51 μmol/L)对于人宫颈癌细胞的抗肿瘤活性优 于 5-氟尿嘧啶(9.51 μmol/L); 化合物 11a～11b 对于所 测五种人类癌细胞的抗肿瘤活性优于化合物 11h～11i, 说明当苯环上引入相同的吸电子基团时, 对位比邻位更 有利于化合物抗肿瘤活性的表达; 当苯环的对位引入不 同的取代基时, 化合物 11a～11c 对于五种人类癌细胞 的抗肿瘤活性优于化合物 11d～11f, 说明苯胺对位为吸 电子取代基比给电子取代基更有利于化合物抗肿瘤活 性的表达; 当 R 为脂肪胺时, 化合物 11l 对于人宫颈癌 细胞的抗肿瘤活性优于化合物 11a～11k, 说明 R 是仲胺 时更有利于化合物抗肿瘤活性的表达; 化合物 11o 对五 种人类癌细胞无抗肿瘤活性, 说明当 R 为不饱和杂环时 不利于其抗肿瘤活性的表达.…”

Synthesis, Cytotoxic Activity Evaluation of Novel 1,2,3‐Triazole Linked Quinazoline Derivatives

“…A series of novel 1,2,3-triazole-quinazoline derivatives were finally obtained in five steps from available anthranilamide and different substituents benzyl chloride. In earlier report, [34] the compound 6 was prepared by the reaction of anthranilamide and carbon disulfide in the presence of potassium hydroxide in ethanol for a long period. In this letter, we also synthesized the compound in a higher yield under the condition of reflux in the presence of potassium hydroxide and excess carbon disulfide in ethanol at 90 ℃ for 5 h. The next part of this synthesis involved the preparation of the compound 7 which was stirred by condensation of compound 6 with propargyl bromide in the mixed solvent of water and dioxane.…”