4-hydroxybenzenesulfonyl chloride -Drug Synthesis Database

【结构式】

【分子编号】54660

【品名】4-hydroxybenzenesulfonyl chloride

【CA登记号】

【分子式】C₆H₅ClO₃S

【分子量】192.6226

【元素组成】C 37.41% H 2.62% Cl 18.41% O 24.92% S 16.65%

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：(VI)

In a different method, sodium 4-hydroxybenzenesulfonate (V) was converted to the sulfonyl chloride (VI) upon treatment with thionyl chloride in hot 1,2-dichloroethane. Reaction of acid chloride (VI) with aniline provided sulfonamide (VII). Alkylation of the phenolic hydroxyl group of (VII) with 3-chloro-3-methyl-1-butyne (VIII) in the presence of DBU and CuCl gave the propargyl ether (IX), which was then cyclized to benzopyran (IV) under Claisen rearrangement conditions.

参考文献中间体

合成目标

【1】 Manley, P.W. (Novartis AG; Novartis Deutschland GmbH); Benzopyrans and pharmaceutical compsns. containing them. EP 0828733; JP 1999505820; US 5905156; WO 9637490 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	54658	2,2-dimethyl-N-phenyl-2H-chromene-6-sulfonamide		C₁₇H₁₇NO₃S	详情	详情
(V)	54659	sodium 4-hydroxybenzenesulfonate		C₆H₅NaO₄S	详情	详情
(VI)	54660	4-hydroxybenzenesulfonyl chloride		C₆H₅ClO₃S	详情	详情
(VII)	54661	4-hydroxy-N-phenylbenzenesulfonamide		C₁₂H₁₁NO₃S	详情	详情
(VIII)	22416	3-chloro-3-methyl-1-butyne	1111-97-3	C₅H₇Cl	详情	详情
(IX)	54662	4-[(1,1-dimethyl-2-propynyl)oxy]-N-phenylbenzenesulfonamide		C₁₇H₁₇NO₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Sulfonylation of methyl 5-bromo-3-methylanthranilate (I) with acid chloride (II) affords sulfonamide (III). Subsequent alkylation of the sulfonamide N of (III) with iodomethane and K2CO3 yields (IV). After protection of the phenolic hydroxyl group of (IV) as the silyl ether (V), benzylic halogenation with N-bromosuccinimide furnishes bromide (VI). Displacement of its benzylic bromide with 1-methylpiperazine (VII) occurs with concomitant desilylation to give (VIII). Mitsunobu coupling of phenol (VIII) with 2-butyn-1-ol (IX) leads to the propargyl ether (X). The methyl ester group of (X) is then hydrolyzed under alkaline conditions to furnish the carboxylic acid (XI).

参考文献中间体

合成目标

【1】 Levin, J.I.; Chen, J.M.; Du, M.T.; Nelson, F.C.; Killar, L.M.; Skala, S.; Sung, A.; Jin, G.; Cowling, R.; Barone, D.; March, C.J.; Mohler, K.M.; Black, R.A.; Skotnicki, J.S.; Anthranilate sulfonamide hydroxamate TACE inhibitors. Part 2: SAR of the acetylenic P1' group. Bioorg Med Chem Lett 2002, 12, 8, 1199.

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)	60447	methyl 2-amino-5-bromo-3-methylbenzoate		C₉H₁₀BrNO₂	详情	详情
(II)	54660	4-hydroxybenzenesulfonyl chloride		C₆H₅ClO₃S	详情	详情
(III)	60448	methyl 5-bromo-2-{[(4-hydroxyphenyl)sulfonyl]amino}-3-methylbenzoate		C₁₅H₁₄BrNO₅S	详情	详情
(IV)	60449	methyl 5-bromo-2-[[(4-hydroxyphenyl)sulfonyl](methyl)amino]-3-methylbenzoate		C₁₆H₁₆BrNO₅S	详情	详情
(V)	60450	methyl 5-bromo-2-[[(4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)sulfonyl](methyl)amino]-3-methylbenzoate		C₂₂H₃₀BrNO₅SSi	详情	详情
(VI)	60451	methyl 5-bromo-3-(bromomethyl)-2-[[(4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)sulfonyl](methyl)amino]benzoate		C₂₂H₂₉Br₂NO₅SSi	详情	详情
(VII)	10061	1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine	109-01-3	C₅H₁₂N₂	详情	详情
(VIII)	60452	methyl 5-bromo-2-[[(4-hydroxyphenyl)sulfonyl](methyl)amino]-3-[(4-methyl-1-piperazinyl)methyl]benzoate		C₂₁H₂₆BrN₃O₅S	详情	详情
(IX)	42514	2-butyn-1-ol	764-01-2	C₄H₆O	详情	详情
(X)	60453	methyl 5-bromo-2-[{[4-(2-butynyloxy)phenyl]sulfonyl}(methyl)amino]-3-[(4-methyl-1-piperazinyl)methyl]benzoate		C₂₅H₃₀BrN₃O₅S	详情	详情
(XI)	60454	5-bromo-2-[{[4-(2-butynyloxy)phenyl]sulfonyl}(methyl)amino]-3-[(4-methyl-1-piperazinyl)methyl]benzoic acid		C₂₄H₂₈BrN₃O₅S	详情	详情

Extended Information