HETEROCYCLIC SUBSTITUTED UREAS .I. IMMUNOSUPPRESSION AND VIRUS INHIBITION BY BENZIMIDAZOLEUREAS
HETEROCYCLIC SUBSTITUTED UREAS .I. IMMUNOSUPPRESSION AND VIRUS INHIBITION BY BENZIMIDAZOLEUREAS
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DOI：
10.1021/jm00306a010
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发表时间：
1969-01-01
影响因子：
7.3
通讯作者：
DELONG, DC
中科院分区：
文献类型：
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作者：
PAGET, CJ;KISNER, K;DELONG, DC
方法R. a-（间三氟甲基苯胺基）苯乙酸。将间-三氟甲基苯胺（12.0g）和邻-溴苯基乙酸（6.5g）的EtOH（100 ml）溶液在100 ℃加热5小时，并在40 ℃蒸发溶剂。将残余物在H2O（100 ml）和Et 5 O（100 ml）之间平衡，并将有机层用IOO-NaOH（三份75 ml）萃取。用Et 3 O反复萃取合并的苛性碱提取物，并通过加入HCl中和。分离出无色油状物，其在静置时结晶。白色晶体（G.方法S. a-（间三氟甲基苯胺基）-对异丙基苯基-乙酸。将对异丙基扁桃酸乙酯（9-0 gi和S（）（“）. 6.0 g）混合，并在初始剧烈反应消退后在100下愈合1小时。在50 ℃下蒸发过量的SO2，得到相当纯的邻硝基化合物（8.5 g.将该物质（8.0 g）和间三氟甲基苯丙氨酸（12.0 g）在100 ℃下搅拌8 h。加入EtOH（100 ml），继续加热2小时。O（100 ml）。将有机溶液依次用2. V HCl和ICO，干燥（Xu 2SO 4），并蒸发。这提供了呈棕色油状物的α-（N-三氟甲基苯胺基）-对异丙基苯基乙酸乙酯（9.7gi.将其溶解于EtOH（10 ml）中并加入到KOH（2.8 g）在ICO（10 ml）中的溶液中。将混合物在温和回流下搅拌3小时，浓缩至一半体积并用DCM（50 ml）稀释。用甲苯（50 ml）萃取澄清的水溶液。通过添加以Kt 2（）为燃料的Fid和ext来中和水溶液。干燥的（Na 2SO 4）2 E12（）溶液经蒸馏得到油状物（7.9g）。后者的研制，
Method R. a-(m-Trifluoromethylanilino) phenylacetic Acid.-A solution of m-trifluoromethylaniliue (12.0 g) and o-bromophenylacetic acid (6.5 g) in EtOH (100 ml) was healed at 100 for 5 hr, and the solvent was evaporated at 40. The residue was equilibrated between H20 (100 ml) and Et5<)(100 ml), and the organic layer was extracted with 10r)-NaOIl (three 75-ml por-tions). The combined caustic extracts were extracted repeatedly with EtsO and neutralized by the addition of HCl. A colorless oil separated which crystallized on standing. as white-crystals (G. Ug).Method S. a-(m-Trifluoromethylanilino)-p-isopropylphenyl-acetic Acid.-Ethyl p-isopropylmandelate (9-0 gi and S ()(']...) 6.0 g) were mixed and healed at 100 for 1 hr after (he initial vigorous reaction had subsided. Evaporation of the excess S (> Ch at 50 yielded t he fairly pure o-ehlnro compound (8.5 gl. This material (8.0 g) and m-trifliiomtnethylaiiiliiie (12.0 gi were stirred at 100 for 8 hi·. EtOH (100 ml) was added and the healing was continued for 2 hr. The EtOH was evaporated and the residue dissolved in Et. O (100 ml). The organic solution was washed successively with 2. V HCl and ICO, dried (Xu2SO,), and evaporated. This affordedethyl a-fzn-trifiuoromethylanilino)-p-isopropylphenylacetate as a brown oil (9.7 gi. This was dissolved in EtOH (10 ml) and added to a solution of KOH (2.8 g) in ICO (10 ml). The mixture was stirred under gentle reflux for 3 hr, concentrated to half-volume and diluted with·> 0 (50 ml). The clearaqueous solution was extracted with toluene (50 ml). The aqueous solul Ion was neutralized by the addition of Fid and ext fueled with Kt2 (). The dried (Na2S () G El2 () solution on evap-oration yielded an oil (7.9 g). Trituration of he latter with