4-methoxy-3-[4-(2,2,2-trichloroacetyl)-1-piperazinyl]benzenesulfonyl chloride -Drug Synthesis Database

【结构式】

【分子编号】48008

【品名】4-methoxy-3-[4-(2,2,2-trichloroacetyl)-1-piperazinyl]benzenesulfonyl chloride

【CA登记号】

【分子式】C₁₃H₁₄Cl₄N₂O₄S

【分子量】436.14204

【元素组成】C 35.8% H 3.24% Cl 32.51% N 6.42% O 14.67% S 7.35%

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：(III)

1-(2-Methoxyphenyl)-4-trichloroacetylpiperazine (II), prepared from 1-(2-methoxyphenyl)piperazine (I) and trichloroacetyl chloride, was treated with chlorosulfonic acid to give the sulfonyl chloride (III). Coupling of chloride (III) with 2,5-dibromo-3-fluoroaniline (IV) afforded sulfonamide (IV). Finally, removal of the trichloroacetyl protecting group under basic conditions provided the title piperazine derivative.

参考文献中间体

合成目标

【2】 Moss, S.F.; Bromidge, S.M. (SmithKline Beecham plc); Novel cpds.. WO 9902502 .
【1】 Bromidge, S.M.; Gager, T.; Clarke, S.E.; et al.; Phenyl benzenesulfonamides are novel and selective 5-HT6 antagonists: Identification of N-(2,5-dibromo-3-fluorophenyl)-4-methoxy-3-piperazin-1-ylbenzenesulfonamide (SB-357134). Bioorg Med Chem Lett 2001, 11, 1, 55.

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)	11882	1-(2-Methoxyphenyl)piperazine; Methyl 2-piperazinophenyl ether; 1-(2-Methoxyphenyl)-piperazine	35386-24-4	C₁₁H₁₆N₂O	详情	详情
(II)	48007	2,2,2-trichloro-1-[4-(2-methoxyphenyl)-1-piperazinyl]-1-ethanone		C₁₃H₁₅Cl₃N₂O₂	详情	详情
(III)	48008	4-methoxy-3-[4-(2,2,2-trichloroacetyl)-1-piperazinyl]benzenesulfonyl chloride		C₁₃H₁₄Cl₄N₂O₄S	详情	详情
(IV)	48009	2,5-dibromo-3-fluoroaniline; 2,5-dibromo-3-fluorophenylamine		C₆H₄Br₂FN	详情	详情
(V)	48010	N-(2,5-dibromo-3-fluorophenyl)-4-methoxy-3-[4-(2,2,2-trichloroacetyl)-1-piperazinyl]benzenesulfonamide		C₁₉H₁₇Br₂Cl₃FN₃O₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

N-(2-Methoxyphenyl)piperazine (I) is protected as the trichloroacetamide (II) using trichloroacetyl chloride and diisopropylethylamine. Then, chlorosulfonation of (II) in cold CH2Cl2 furnishes sulfonyl chloride (III)

参考文献中间体

合成目标

【1】 Bromidge, S.M.; Moss, S.F. (GlaxoSmithKline plc); N-(3,5-Dichloro-2-methoxyphenyl)-4-methoxy-3-piperazin-1-yl-benzenesulfonamide. EP 1313720; WO 0218358 .

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)	11882	1-(2-Methoxyphenyl)piperazine; Methyl 2-piperazinophenyl ether; 1-(2-Methoxyphenyl)-piperazine	35386-24-4	C₁₁H₁₆N₂O	详情	详情
(II)	48007	2,2,2-trichloro-1-[4-(2-methoxyphenyl)-1-piperazinyl]-1-ethanone		C₁₃H₁₅Cl₃N₂O₂	详情	详情
(III)	48008	4-methoxy-3-[4-(2,2,2-trichloroacetyl)-1-piperazinyl]benzenesulfonyl chloride		C₁₃H₁₄Cl₄N₂O₄S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

Alkylation of 2,4-dichloro-6-nitrophenol (IV) with iodomethane in the presence of K2CO3 provides the methyl ether (V). Subsequent nitro group reduction in (V) employing iron powder and NH4Cl leads to aniline (VI). This is then acylated by sulfonyl chloride (III) to form sulfonamide (VII). The N-trichloroacetyl group of (VII) is finally removed by alkaline hydrolysis to provide the title compound

参考文献中间体

合成目标

【1】 Bromidge, S.M.; Moss, S.F. (GlaxoSmithKline plc); N-(3,5-Dichloro-2-methoxyphenyl)-4-methoxy-3-piperazin-1-yl-benzenesulfonamide. EP 1313720; WO 0218358 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(III)	48008	4-methoxy-3-[4-(2,2,2-trichloroacetyl)-1-piperazinyl]benzenesulfonyl chloride	C₁₃H₁₄Cl₄N₂O₄S	详情	详情
(IV)	60881	2,4-dichloro-6-nitrophenol	C₆H₃Cl₂NO₃	详情	详情
(V)	60882	2,4-dichloro-6-nitrophenyl methyl ether; 1,5-dichloro-2-methoxy-3-nitrobenzene	C₇H₅Cl₂NO₃	详情	详情
(VI)	60883	3,5-dichloro-2-methoxyaniline; 3,5-dichloro-2-methoxyphenylamine	C₇H₇Cl₂NO	详情	详情
(VII)	60884	N-(3,5-dichloro-2-methoxyphenyl)-4-methoxy-3-[4-(2,2,2-trichloroacetyl)-1-piperazinyl]benzenesulfonamide	C₂₀H₂₀Cl₅N₃O₅S	详情	详情

Extended Information