methyl 5-bromo-2-[{[4-(2-butynyloxy)phenyl]sulfonyl}(methyl)amino]-3-[(4-methyl-1-piperazinyl)methyl]benzoate -Drug Synthesis Database

【结构式】

【分子编号】60453

【品名】methyl 5-bromo-2-[{[4-(2-butynyloxy)phenyl]sulfonyl}(methyl)amino]-3-[(4-methyl-1-piperazinyl)methyl]benzoate

【CA登记号】

【分子式】C₂₅H₃₀BrN₃O₅S

【分子量】564.50042

【元素组成】C 53.19% H 5.36% Br 14.15% N 7.44% O 14.17% S 5.68%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(X)

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