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【结 构 式】 
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【药物名称】 【化学名称】5-[1-[4-[6-(2-Chlorophenyl)-1,4-dimethyl-7,8,9,10-tetrahydro-4H-pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-9-ylcarbonylphenyl]-1-(3-pyridyl)methylideneaminooxy]pentanoic acid ethyl ester 【CA登记号】218152-77-3 【 分 子 式 】C39H38ClN7O4S 【 分 子 量 】736.29921 |
【开发单位】Nikken Chemicals (Originator) 【药理作用】Antiallergy/Antiasthmatic Drugs, ANTIINFECTIVE THERAPY, Antiplatelet Therapy, Asthma Therapy, Cerebrovascular Diseases, Treatment of, Coagulation Disorders Therapy, HEMATOLOGIC DRUGS, NEUROLOGIC DRUGS, RESPIRATORY DRUGS, Stroke, Treatment of, Treatment of Septic Shock, Platelet-Activating Factor (PAF) Antagonists, Thromboxane Synthase Inhibitors |
合成路线1
Treatment of 4-(t-butyldiphenylsilyloxymethyl)phenyl-(3-pyridyl)ketone (I) with hydroxylamine hydrochloride in pyridine affords oxime (II) as a mixture of geometric isomers. Then, alkylation of oxime (II) with ethyl 5-bromovalerate (III) in the presence of NaH provides ester (IV). After desilylation of (IV) with tetrabutylammonium fluoride, the deprotected primary alcohol (V) is oxidized by KMnO4 to furnish carboxylic acid (VI). Finally, DCC-mediated coupling of acid (VI) with the known tetracyclic precursor (VII) gives rise to the corresponding amide.
| 【1】 Sano, T.; Seki, T.; Fujita, M.; Inada, H. (Nikken Chemicals Co., Ltd.); Triazolo-1,4-diazepine cpds. and medicinal compsn. containing the same. EP 0995752; JP 1999071378; US 6433167; WO 9858930 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 54466 | [4-({[tert-butyl(diphenyl)silyl]oxy}methyl)phenyl](3-pyridinyl)methanone | C29H29NO2Si | 详情 | 详情 | |
| (II) | 61007 | [4-({[tert-butyl(diphenyl)silyl]oxy}methyl)phenyl](3-pyridinyl)methanone oxime | C29H30N2O2Si | 详情 | 详情 | |
| (III) | 37151 | ethyl 5-bromopentanoate | 14660-52-7 | C7H13BrO2 | 详情 | 详情 |
| (IV) | 61008 | ethyl 5-({[(E)-[4-({[tert-butyl(diphenyl)silyl]oxy}methyl)phenyl](3-pyridinyl)methylidene]amino}oxy)pentanoate | C36H42N2O4Si | 详情 | 详情 | |
| (V) | 61009 | ethyl 5-({[(E)-[4-(hydroxymethyl)phenyl](3-pyridinyl)methylidene]amino}oxy)pentanoate | C20H24N2O4 | 详情 | 详情 | |
| (VI) | 61010 | 4-[{[(5-ethoxy-5-oxopentyl)oxy]imino}(3-pyridinyl)methyl]benzoic acid | C20H22N2O5 | 详情 | 详情 | |
| (VII) | 14057 | 6-(2-Chlorophenyl)-1,4-dimethyl-7,8,9,10-tetrahydro-4H-pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine | C19H18ClN5S | 详情 | 详情 |