Israpafant, Y-24180, Pafnol
伊拉帕泛Chemical Name: (?-4-(2-Chlorophenyl)-2-[2-(4-isobutylphenyl)ethyl]-6,9-dimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine
CAS No. 117279-73-9
项目整合开发状态: Phase III
项目研究机构: Mitsubishi Pharma (Originator)
合成路线:Reaction of 2-(2-chlorobenzoyl)acetonitrile (I) with 4-(4-isobutylphenyl)butyraldehyde (II) and sulfur in DMF/NEt3 gives 2-amino-3-(2-chlorobenzoyl)-5-[2-(4-isobutylphenyl)ethyl]thiophene (III),which is acylated with 2-chloropropionyl chloride (IV) in chloroform to give 2-(2-chloropropionamido)-3-(2-chlorobenzoyl)-5-[2-(4-isobutylphenyl) ethyl]thiophene (V).Compound (V) is treated with sodium iodide in THF followed by liquid ammonia to give 2-(2-aminopropionamido)-3-(2-chlorobenzoyl)-5-[2-(4-isobutylphenyl) ethyl]thiophene (VI),which is cyclized in isopropanol and acetic acid to give 5-(2-chlorophenyl)-5-[2-(4-isobutylphenyl)ethyl]-3-methyl-2,3-dihydro-1H-thieno[2,3-e]-1,4-diazepin-2-one (VII).Compound (VII) gives 5-(2-chlorophenyl)-7-[2-(4-isobutylphenyl)ethyl]-3-methyl-2,3-dihydro-1H-thieno[2,3-e]-1,4-diazepin-2-thione (VIII) upon treatment with Lawesson's reagent.Finally,(VIII) is cyclized with hydrazine hydrate and ethyl orthoformiate.
📌 参考资料/链接：
参考文献标题:PAF-antagonistic thienotriazolodiazepine compounds and pharmaceutical uses thereof
文献作者:Tahara,T.; Moriwaki,M.; Abe,M.; Yuasa,S.(Welfide Corporation)
参考来源:EP 0268242; JP 1989156982; US 4820703
📄 详细内容
合成路线:Reaction of 2-(2-chlorobenzoyl)acetonitrile (I) with 4-(4-isobutylphenyl)butyraldehyde (II) and sulfur in DMF/NEt3 gives 2-amino-3-(2-chlorobenzoyl)-5-[2-(4-isobutylphenyl)ethyl]thiophene (III),which is acylated with 2-chloropropionyl chloride (IV) in chloroform to give 2-(2-chloropropionamido)-3-(2-chlorobenzoyl)-5-[2-(4-isobutylphenyl) ethyl]thiophene (V).Compound (V) is treated with sodium iodide in THF followed by liquid ammonia to give 2-(2-aminopropionamido)-3-(2-chlorobenzoyl)-5-[2-(4-isobutylphenyl) ethyl]thiophene (VI),which is cyclized in isopropanol and acetic acid to give 5-(2-chlorophenyl)-5-[2-(4-isobutylphenyl)ethyl]-3-methyl-2,3-dihydro-1H-thieno[2,3-e]-1,4-diazepin-2-one (VII).Compound (VII) gives 5-(2-chlorophenyl)-7-[2-(4-isobutylphenyl)ethyl]-3-methyl-2,3-dihydro-1H-thieno[2,3-e]-1,4-diazepin-2-thione (VIII) upon treatment with Lawesson's reagent.Finally,(VIII) is cyclized with hydrazine hydrate and ethyl orthoformiate.
参考文献标题:Y-24180
文献作者:Castar,J.; Prous,J.; Mealy,N.
参考来源:Drugs Fut 1993,18(11),1016
合成路线:A new synthesis of Y-24180 has been published:The reaction of 2-(2-chlorobenzoyl)acetonitrile (I) with 4-(4-isobutylphenyl)butyraldehyde (II) and sulfur by means of triethylamine in DMF gives the benzoylthiophene (III),which is condensed with 2-phthalimidopropionyl chloride (IV) yielding the propionamidothiophene (V).Elimination of the phthalimido group of (V) first with hydrazine and then with HCl affords the alanylaminothiophene (VI),which is cyclized by means of acetic acid giving 5-(2-chlorophenyl)-7-[2-(4-isobutylphenyl)ethyl]-3-methyl-2,3-dihydro-1 H-thieno[3,2-f][1,4]diazepin-2-one (VII).The reaction of (VII) with P2S5 yields the corresponding thioketone (VIII),which by reaction with hydrazine is converted into the hydrazone (IX).Finally,this compound is cyclized with triethyl orthoacetate (X).
参考文献标题:Structural optimization of 4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepines as antagonists for platelet activating factor: Pharmacological contribution of substituents at the 2- and 6-positions of a condensed ring system
文献作者:Kawakami,Y.; Moriwaki,M.; Kitani,H.; Kagoshima,M.; Abe,M.; Tahara,T.; Terasawa,M.; Yuasa,S.
参考来源:Eur J Med Chem 1996,31(9),683
产品链接: CAS No. 117279-73-9››