2-ethyl-1lambda~6~-isothiazolidine-1,1-dione -Drug Synthesis Database

【结构式】

【分子编号】59785

【品名】2-ethyl-1lambda~6~-isothiazolidine-1,1-dione

【CA登记号】

【分子式】C₅H₁₁NO₂S

【分子量】149.21388

【元素组成】C 40.25% H 7.43% N 9.39% O 21.44% S 21.49%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(III)

The intermediate gamma-sultam (III) was prepared by condensation of 3-chloropropylsulfonyl chloride (I) with ethylamine, followed by cyclization of the resulting chloro sulfonamide (II) under basic conditions. Condensation of 3,5-di-tert-butyl-4-(methoxymethoxy)benzaldehyde (IV) with sultam (III) in the presence of LDA produced the aldol addition compound (V). Then, acid-promoted dehydration and simultaneous methoxymethyl group deprotection gave rise to a mixture of the desired E-benzylidene sultam and the corresponding Z-isomer (VII), which were separated by column chromatography.

参考文献中间体

合成目标

【1】 Inagaki, M.; Tsuri, T.; Jyoyama, H.; yamada, K.; Ono, T.; Matsumoto, S.; A novel antiarthritic agent S-2474: Synthesis and pharmacological effects. 17th Symp Med Chem (Nov 19 1997, Tsukuba) 1997, Abst 2-P-25.
【2】 Matsumoto, S.; Tsuri, T.; Inagaki, M.; Jyoyama, H. (Shionogi & Co. Ltd.); Benzylidene derivs.. EP 0595546; JP 1994211819; US 5418230 .
【3】 Inagaki, M.; Tsuri, T.; Jyoyama, H.; et al.; Novel antiarthritic agents with 1,2-isothiazolidine-1,1-dioxide (gamma-sultam) skeleton: Cytokine suppressive dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase. J Med Chem 2000, 43, 10, 2040.

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)	39225	g-Chloropropanesulfonyl chloride;3-Chloropropansulfonyl chloride;1-Chloro-3-propanesulfonylchloride;3-Chloropropanesulfonyl chloride;3-chloro-1-propanesulfonyl chloride;3-chloropropane-1-sulfonyl chloride	1633-82-5	C₃H₆Cl₂O₂S	详情	详情
(II)	59784	3-chloro-N-ethyl-1-propanesulfonamide		C₅H₁₂ClNO₂S	详情	详情
(III)	59785	2-ethyl-1lambda~6~-isothiazolidine-1,1-dione		C₅H₁₁NO₂S	详情	详情
(IV)	59786	3,5-di(tert-butyl)-4-(methoxymethoxy)benzaldehyde		C₁₇H₂₆O₃	详情	详情
(V)	59787	5-[[3,5-di(tert-butyl)-4-(methoxymethoxy)phenyl](hydroxy)methyl]-2-ethyl-1lambda~6~-isothiazolidine-1,1-dione		C₂₂H₃₇NO₅S	详情	详情
(VII)	59788	5-{(Z)-[3,5-di(tert-butyl)-4-hydroxyphenyl]methylidene}-2-ethyl-1lambda~6~-isothiazolidine-1,1-dione		C₂₀H₃₁NO₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

An improved synthesis has been reported. Acid-catalyzed ketalization of aldehyde (VIII) with trimethyl orthoformate provided the dimethyl acetal (IX) which, upon thermal decomposition in refluxing xylene, gave rise to the alpha-methoxy methylenequinone derivative (X). This was then condensed with the lithio derivative of sultam (III) to form selectively the desired E-adduct. In an analogous procedure, aldehyde (VIII) was converted to the chloromethylene compound (XI) with methanesulfonyl chloride and triethylamine in refluxing CH2Cl2. Condensation of (XI) with the lithiated sultam (III) furnished the desired E-benzylidene sultam.

参考文献中间体

合成目标

【1】 Inagaki, M.; Haga, N.; Kobayashi, M.; Ohta, N.; Kamata, S.; Tsuri, T.; Highly E-selective and effective synthesis of antiarthritic drug candidate S-2474 using quinone methide derivatives. J Org Chem 2002, 67, 1, 125.
【2】 Haga, N.; Inagaki, M.; Matsumoto, S.; Kamata, S. (Shionogi & Co. Ltd.); Method for producing benzylidene derivs.. EP 0626377 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(III)	59785	2-ethyl-1lambda~6~-isothiazolidine-1,1-dione		C₅H₁₁NO₂S	详情	详情
(VIII)	14875	3,5-Bis(1,1-dimethylethyl)-4-hydroxybenzaldehyde; 3,5-di(tert-butyl)-4-hydroxybenzaldehyde; 3,5-Di-tert-butyl-4-hydroxybenzaldehyde	1620-98-0	C₁₅H₂₂O₂	详情	详情
(IX)	59789	2,6-di(tert-butyl)-4-(dimethoxymethyl)phenol		C₁₇H₂₈O₃	详情	详情
(X)	59790	2,6-di(tert-butyl)-4-(methoxymethylene)-2,5-cyclohexadien-1-one		C₁₆H₂₄O₂	详情	详情
(XI)	59791	2,6-di(tert-butyl)-4-methylene-2,5-cyclohexadien-1-one		C₁₅H₂₂O	详情	详情

Extended Information