Zalospirone hydrochloride, Wy-47846, -Drug Synthesis Database

【结构式】

【药物名称】Zalospirone hydrochloride, Wy-47846

【化学名称】3a,4,4a,6a,7,7a-Hexahydro-2-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-4,7-etheno-1H-cyclobut[f]isoindole-1,3(2H)-dione hydrochloride
　　　　　　endo-(3aalpha,4alpha,4abeta,6abeta,7alpha,7aalpha)-Hexahydro-2-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-4,7-etheno-1H-cyclobut[f]isoindole-1,3(2H)-dione hydrochloride
　　　　　　(1R*,2R*,5S*,6S*,7S*,8R*)-N-[4-[4-(2-Pyrimidinyl)-1-piperazinyl]butyl]tricyclo[4.2.2.0(2,5)]deca-3,9-diene-7,8-dicarboximide hydrochloride

【CA登记号】110944-55-3, 114298-18-9 (free base;no stereoch.), 114374-97-9 (undefined stereoch.)

【分子式】C₂₄H₃₀ClN₅O₂

【分子量】455.992

【开发单位】Wyeth Pharmaceuticals (Originator)

【药理作用】Antidepressants, Anxiolytics, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS, 5-HT1A Receptor Agonists

合成路线1

Reaction of 1,3,5,7-cyclooctatetraene (I) with maleimide (Step a, b), or maleic anhydride (Step c), in refluxing toluene affords the imide (II) or the anhydride (III) in 78 and 85% yields, respectively. Reaction of imide intermediate (II) with 1,4-dibromobutane gives the omega-haloalkylimide, which subsequently is reacted with 1-(2-pyrimidinyl)piperazine to yield Wy-47846 (Method A). Alternatively, Wy-47846 can be prepared via the reaction of (III) with 1-(4-aminobutyl)-4-(2-pyrimidinyl)piperazine in refluxing pyridine (Method B), as shown in scheme. Wy-47846 is achiral.

参考文献中间体

【2】 Abou-Gharbia, M.; Moyer, J.A.; Haskins, J.T.; WY-47846. Drugs Fut 1989, 14, 5, 442.
【1】 Abou-Gharbia, M.; et al.; Polycyclic aryl- and heteroarylpiperazyl imides as 5-HT1A receptor ligands and potential anxiolytic agents: synthesis and structure-activity relationship studies. J Med Chem 1988, 31, 7, 1382.

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)	20923	1,3,5,7-cyclooctatetraene	629-20-9	C₈H₈	详情	详情
(II)	20924	bicyclo[4.2.0]octa-2,4-diene		C₈H₁₀	详情	详情
(III)	20925	(2R,6S,8R,11S)-4-azatetracyclo[5.4.2.0(2,6).0(8,11)]trideca-9,12-diene-3,5-dione		C₁₂H₁₁NO₂	详情	详情
(IV)	20926	(2R,6S,8R,11S)-4-oxatetracyclo[5.4.2.0(2,6).0(8,11)]trideca-9,12-diene-3,5-dione		C₁₂H₁₀O₃	详情	详情
(V)	19711	1H-pyrrole-2,5-dione	541-59-3	C₄H₃NO₂	详情	详情
(VI)	11182	2,5-Furandione; Maleic anhydride	108-31-6	C₄H₂O₃	详情	详情
(VII)	11883	1,4-Dibromobutane; 1,4-Butylene bromide	110-52-1	C₄H₈Br₂	详情	详情
(VIII)	11175	2-(1-Piperazinyl)pyrimidine; 2-Piperazinopyrimidine; N-(Pyrimidinyl)piperazine	20980-22-7	C₈H₁₂N₄	详情	详情
(IX)	11181	4-[4-(2-Pyrimidinyl)piperazino]butylamine; 4-[4-(2-Pyrimidinyl)piperazino]-1-butanamine	33386-20-8	C₁₂H₂₁N₅	详情	详情

Extended Information