S-31354, -Drug Synthesis Database

【结构式】

【药物名称】S-31354

【化学名称】3-[6-(4-Chlorophenylsulfonamido)-2-(2-nitrooxyethyl)-5,6,7,8-tetrahydro-1-naphthyl]propionic acid

【CA登记号】213313-90-7

【分子式】C₂₁H₂₃ClN₂O₇S

【分子量】482.94366

【开发单位】Servier (Originator)

【药理作用】Antiplatelet Therapy, Atherosclerosis Therapy, CARDIOVASCULAR DRUGS, Coagulation Disorders Therapy, HEMATOLOGIC DRUGS, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, Nitric Oxide Donors, Prostanoid TP (Thromboxane A2) Antagonists

合成路线1 合成路线2

合成路线1

Diels-Alder condensation of benzopyran (I) with methyl (trimethylsilyl)propynoate (II) gave rise to tetrahydronaphthalene (III). After reduction of the ester group of (III) with LiAlH4, the resulting alcohol (IV) was further oxidized to aldehyde (V) by means of 4-benzylpyridinium dichromate. Treatment of (V) with iodine monochloride produced iodonaphthalene (VI). Subsequent reaction of (VI) with vinyl tributyltin and palladium tetrakis(triphenylphosphine) yielded the vinyl naphthalene (VII). Wittig reaction of (VIII with (carbomethoxymethylidene)triphenylphosphorane (VIII) gave the arylpropenoate ester (IX), which was reduced to the saturated ester (X) employing samarium iodide.

参考文献中间体

【1】 Lavielle, G.; Cimetiere, B.; Verbeuren, T.; Simonet, S.; Descombes, J.-J. (ADIR et Cie.); Nouveaux dérivés de benzènsessulfonylamine, leur procédé depréparation et les compositions pharmaceutiques qui les contiennent. EP 0864561 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	24920	tributyl(vinyl)stannane；Tributylvinylstannane;Vinyltributylstannane	7486-35-3	C₁₄H₃₀Sn	详情	详情
(I)	19586	4-chloro-N-(2-oxo-5,6,7,8-tetrahydro-2H-chromen-6-yl)benzenesulfonamide		C₁₅H₁₄ClNO₄S	详情	详情
(II)	32594	methyl 3-(trimethylsilyl)-2-propynoate		C₇H₁₂O₂Si	详情	详情
(III)	32595	methyl 6-[[(4-chlorophenyl)sulfonyl]amino]-2-(trimethylsilyl)-5,6,7,8-tetrahydro-1-naphthalenecarboxylate		C₂₁H₂₆ClNO₄SSi	详情	详情
(IV)	32596	4-chloro-N-[5-(hydroxymethyl)-6-(trimethylsilyl)-1,2,3,4-tetrahydro-2-naphthalenyl]benzenesulfonamide		C₂₀H₂₆ClNO₃SSi	详情	详情
(V)	32597	4-chloro-N-[5-formyl-6-(trimethylsilyl)-1,2,3,4-tetrahydro-2-naphthalenyl]benzenesulfonamide		C₂₀H₂₄ClNO₃SSi	详情	详情
(VI)	19571	4-chloro-N-(5-formyl-6-iodo-1,2,3,4-tetrahydro-2-naphthalenyl)benzenesulfonamide		C₁₇H₁₅ClINO₃S	详情	详情
(VII)	32598	4-chloro-N-(5-formyl-6-vinyl-1,2,3,4-tetrahydro-2-naphthalenyl)benzenesulfonamide		C₁₉H₁₈ClNO₃S	详情	详情
(VIII)	14689	Methyl (triphenylphosphoranylidene)acetate; (methoxycarbonylmethylene)triphenylphosphorane；Methyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate	2605-67-6	C₂₁H₁₉O₂P	详情	详情
(IX)	32599	methyl (E)-3-(6-[[(4-chlorophenyl)sulfonyl]amino]-2-vinyl-5,6,7,8-tetrahydro-1-naphthalenyl)-2-propenoate		C₂₂H₂₂ClNO₄S	详情	详情
(X)	32600	methyl 3-(6-[[(4-chlorophenyl)sulfonyl]amino]-2-vinyl-5,6,7,8-tetrahydro-1-naphthalenyl)propanoate		C₂₂H₂₄ClNO₄S	详情	详情

合成路线2

Hydroboration of the vinyl group of (X), followed by oxidative treatment with sodium perborate furnished alcohol (XI), which was further activated as the corresponding tosylate (XII). Displacement of the tosylate group of (XII) with tetrabutylammonium nitrate in toluene gave nitrate ester (XIII). The methyl ester group of (XIII) was finally hydrolyzed with NaOH to the target carboxylic acid.

参考文献中间体

【1】 Lavielle, G.; Cimetiere, B.; Verbeuren, T.; Simonet, S.; Descombes, J.-J. (ADIR et Cie.); Nouveaux dérivés de benzènsessulfonylamine, leur procédé depréparation et les compositions pharmaceutiques qui les contiennent. EP 0864561 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(X)	32600	methyl 3-(6-[[(4-chlorophenyl)sulfonyl]amino]-2-vinyl-5,6,7,8-tetrahydro-1-naphthalenyl)propanoate	C₂₂H₂₄ClNO₄S	详情	详情
(XI)	32601	methyl 3-[6-[[(4-chlorophenyl)sulfonyl]amino]-2-(2-hydroxyethyl)-5,6,7,8-tetrahydro-1-naphthalenyl]propanoate	C₂₂H₂₆ClNO₅S	详情	详情
(XII)	32602	methyl 3-[6-[[(4-chlorophenyl)sulfonyl]amino]-2-(2-[[(4-methylphenyl)sulfonyl]oxy]ethyl)-5,6,7,8-tetrahydro-1-naphthalenyl]propanoate	C₂₉H₃₂ClNO₇S₂	详情	详情
(XIII)	32603	methyl 3-[6-[[(4-chlorophenyl)sulfonyl]amino]-2-[2-(nitrooxy)ethyl]-5,6,7,8-tetrahydro-1-naphthalenyl]propanoate	C₂₂H₂₅ClN₂O₇S	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(2)