Chlorosulfonic acid -Drug Synthesis Database

【结构式】

【分子编号】29008

【品名】Chlorosulfonic acid

【CA登记号】7790-94-5

【分子式】HClO₃S

【分子量】116.52484

【元素组成】H 0.87% Cl 30.43% O 41.19% S 27.52%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(VIII)

The acetylation of 1,2,3,4-tetrahydroisoquinoline (I) with acetic anhydride gives 2-acetyl-1,2,3,4-tetrahydroisoquinoline (II), which is sulfonated with chloro sulfonic acid in methylene chloride yielding 2-acetyl-7-chlorosulfonyl-1,2,3,4-tetrahydroisoquinoline (III). The reaction of (III) with 3-chloroaniline (IV) and triethylamine in refluxing acetone affords 2-acetyl-7-(3-chlorophenylamino sulfonyl)-1,2,3,4-tetrahydroisoquinoline (V), which is deacetylated by a treatment with HCl in refluxing butanol to 7-(3-chlorophenylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline (VI). Finally, this compound is condensed with bis(chlorosulfonyl)imide (VII) [prepared with chlorosulfonic acid (VIII) and chlorosulfonyl isocyanate (IX)] in acetonitrile containing triethylamine.

参考文献中间体

合成目标

【1】 Ali Fadia E. (SmithKline Beecham Corp.); N,N'-Bis[substituted-1,2,3,4-tetrahydroisoquinolino]disulfonylimides and antiallergic compositions and method of use. DD 158240; EP 0038177; US 4135935 .
【2】 Serradell, M.N.; Chu, S.S.; Castaner, J.; SKF-88046. Drugs Fut 1985, 10, 1, 42.

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)	14124	1,2,3,4-Tetrahydroisoquinoline	91-21-4	C₉H₁₁N	详情	详情
(II)	29003	1-[3,4-dihydro-2(1H)-isoquinolinyl]-1-ethanone		C₁₁H₁₃NO	详情	详情
(III)	29004	2-acetyl-1,2,3,4-tetrahydro-7-isoquinolinesulfonyl chloride		C₁₁H₁₂ClNO₃S	详情	详情
(IV)	25239	3-chloroaniline; 3-chlorophenylamine	108-42-9	C₆H₆ClN	详情	详情
(V)	29005	2-acetyl-N-(3-chlorophenyl)-1,2,3,4-tetrahydro-7-isoquinolinesulfonamide		C₁₇H₁₇ClN₂O₃S	详情	详情
(VI)	29006	N-(3-chlorophenyl)-1,2,3,4-tetrahydro-7-isoquinolinesulfonamide		C₁₅H₁₅ClN₂O₂S	详情	详情
(VII)	29007	Bis(chlorosulfonyl)imide		HCl₂NO₄S₂	详情	详情
(VIII)	29008	Chlorosulfonic acid	7790-94-5	HClO₃S	详情	详情
(IX)	14101	Chlorosulfonyl isocyanate	1189-71-5	CClNO₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：

The acetylation of 3,5-dimethylaniline (I) with acetic anhydride gives the acetamide (II), which is treated with chlorosulfonic acid yielding the benzenesulfonyl chloride (III). The reduction of (III) with Na2SO3 and NaHCO3 in water affords the sulfinic acid (IV), which by reaction with sodium methoxide in methanol gives the corresponding sodium salt (V). The reaction of (V) with nitromethane and sodium methoxide yields the sulfonylnitromethane (VI), which is deacetylated with hot 2N NaOH affording 3,5-dimethyl-4-(nitromethylsulfonyl)aniline (VII). Finally, this compound is treated with thiophosgene in acetone to provide the target isothiocyanate.

参考文献中间体

合成目标

【1】 Rodriguez, L.; Miller, D.D.; Kador, P.F.; Saab, N.H.; Donkor, I.O.; Phenylsulfonylnitromethasanes as potent irreversible inhibitors of aldose reductase. Eur J Med Chem 1999, 34, 9, 745.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	29008	Chlorosulfonic acid	7790-94-5	HClO₃S	详情	详情
	39563	nitromethane	75-52-5	CH₃NO₂	详情	详情
(I)	18431	3,5-dimethylaniline; 3,5-dimethylphenylamine	108-69-0	C₈H₁₁N	详情	详情
(II)	31521	N-(3,5-dimethylphenyl)acetamide		C₁₀H₁₃NO	详情	详情
(III)	31596	4-(acetamido)-2,6-dimethylbenzenesulfonyl chloride		C₁₀H₁₂ClNO₃S	详情	详情
(IV)	31597	N-[4-(dioxo-lambda(6)-sulfanyl)-3,5-dimethylphenyl]acetamide		C₁₀H₁₃NO₃S	详情	详情
(V)	31598	[[4-(acetamido)-2,6-dimethylphenyl]sulfonyl]sodium		C₁₀H₁₂NNaO₃S	详情	详情
(VI)	31599	N-[3,5-dimethyl-4-[(nitromethyl)sulfonyl]phenyl]acetamide		C₁₁H₁₄N₂O₅S	详情	详情
(VII)	31600	3,5-dimethyl-4-[(nitromethyl)sulfonyl]aniline; 3,5-dimethyl-4-[(nitromethyl)sulfonyl]phenylamine		C₉H₁₂N₂O₄S	详情	详情

合成路线3

该中间体在本合成路线中的序号：

The intermediate sulfonyl chloride (IV) was prepared by condensation of phenyl isocyanate (I) with n-hexylamine (II), followed by chlorosulfonation of the resulting hexyl phenyl urea (III) with ClSO3H at 60 C.

参考文献中间体

合成目标

【1】 Fisher, M.H.; Naylor, E.M.; Ok, D.; Weber, A.E.; Shih, T.; Ok, H. (Merck & Co., Inc.); Substd. sulfonamides as selective beta3 agonists for the treatment of diabetes and obesity. EP 0757674; JP 1997512275; US 5541197; US 5561142; WO 9529159 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	29008	Chlorosulfonic acid	7790-94-5	HClO₃S	详情	详情
(I)	11289	1-Isocyanatobenzene; phenyl isocyanate; Phenylisocyanate	103-71-9	C₇H₅NO	详情	详情
(II)	26546	n-hexylamine; hexylamine	111-26-2	C₆H₁₅N	详情	详情
(III)	26547	N-hexyl-N'-phenylurea		C₁₃H₂₀N₂O	详情	详情
(IV)	26548	4-[[(hexylamino)carbonyl]amino]benzenesulfonyl chloride		C₁₃H₁₉ClN₂O₃S	详情	详情

Extended Information