4-Aminobenzenesulfonamide; p-Aminobenzene sulfonyl amide; p-Aminobenzenesulfonamide; p-Anilinesulfonamide; Sulfanilamide -Drug Synthesis Database

【结构式】

【分子编号】54719

【品名】4-Aminobenzenesulfonamide; p-Aminobenzene sulfonyl amide; p-Aminobenzenesulfonamide; p-Anilinesulfonamide; Sulfanilamide

【CA登记号】63-74-1

【分子式】C₆H₈N₂O₂S

【分子量】172.2078

【元素组成】C 41.85% H 4.68% N 16.27% O 18.58% S 18.62%

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：(V)

The reaction of 7-nitro-1H-indole (I) with NCS in acetonitrile gives 3-chloro-7-nitro-1H-indole (II), which is reduced with Fe and NH4Cl or stannous chloride in ethanol/aq. HCl to yield 3-chloro-1H-indol-7-amine (III). Finally, this compound is condensed with 4-sulfamoylbenzenesulfonyl chloride (IV) in pyridine to afford the target sulfonamide. The intermediate 4-sulfamoylbenzenesulfonyl chloride (IV) is obtained by diazotation of 4-aminobenzenesulfonamide (V) with NaNo2 and HCl, followed by treatment with SO2 and CuCl2.

参考文献中间体

合成目标

【1】 Yoshino, H.; Yamato, T.; Okauchi, T.; Yoshimatsu, K.; Sugi, N.; Nagasu, T.; Ozawa, Y.; Koyanagi, N.; Kito, K. (Eisai Co., Ltd.); Bicyclic heterocyclic sulfonamide and sulfonic ester derivs.. EP 0673937; US 5721246; WO 9507276 .

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)	54715	7-Nitroindole	6960-42-5	C₈H₆N₂O₂	详情	详情
(II)	54716	3-chloro-7-nitro-1H-indole		C₈H₅ClN₂O₂	详情	详情
(III)	54717	3-chloro-1H-indol-7-amine; 3-chloro-1H-indol-7-ylamine		C₈H₇ClN₂	详情	详情
(IV)	54718	4-(aminosulfonyl)benzenesulfonyl chloride		C₆H₆ClNO₄S₂	详情	详情
(V)	54719	4-Aminobenzenesulfonamide; p-Aminobenzene sulfonyl amide; p-Aminobenzenesulfonamide; p-Anilinesulfonamide; Sulfanilamide	63-74-1	C₆H₈N₂O₂S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Diazotization of sulfanilamide (I), followed by treatment of the resultant diazonium salt with potassium cyanide/copper sulfate under Sandmeyer conditions, leads to nitrile (II). Stephen reduction of (II) with Raney nickel alloy in 75% aqueous formic acid gives the benzaldehyde (III), which is further reduced to the benzyl alcohol (IV) using NaBH4 in ethanol. Treatment of alcohol (IV) with PBr3 provides the benzyl bromide (V). This is then subjected to Arbuzov reaction with triethyl phosphite to produce phosphonate (VI). Finally, Wittig-Horner condensation of (VI) with 4-fluorobenzaldehyde (VII) furnishes the target stilbene derivative.

参考文献中间体

合成目标

【1】 Lin, S.-J.; Hsu, F.-L.; Yang, T.-H.; Yang, L.-M.; Antitumor agents. Part 3: Synthesis and cytotoxicity of new trans-stilbene benzenesulfonomide derivatives. Bioorg Med Chem Lett 2002, 12, 7, 1013.

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)	54719	4-Aminobenzenesulfonamide; p-Aminobenzene sulfonyl amide; p-Aminobenzenesulfonamide; p-Anilinesulfonamide; Sulfanilamide	63-74-1	C₆H₈N₂O₂S	详情	详情
(II)	58874	4-Cyanobenzenesulphonamide		C₇H₆N₂O₂S	详情	详情
(III)	58875	4-formylbenzenesulfonamide		C₇H₇NO₃S	详情	详情
(IV)	58876	4-(hydroxymethyl)benzenesulfonamide		C₇H₉NO₃S	详情	详情
(V)	58877	4-(bromomethyl)benzenesulfonamide		C₇H₈BrNO₂S	详情	详情
(VI)	58878	diethyl 4-(aminosulfonyl)benzylphosphonate		C₁₁H₁₈NO₅PS	详情	详情
(VII)	12337	4-fluorobenzaldehyde	459-57-4	C₇H₅FO	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VI)

In one strategy, bromination of 4-ethoxyacetophenone (I) with Br2 yields 2-bromo-1-(4-ethoxyphenyl)ethanone (II) along with the byproduct 2-bromo-1-(3-bromo-4-ethoxyphenyl)ethanone, which are separated using HPLC. Alkylation of propionaldehyde N,N-diisobutylenamine (III) with bromo ketone (II) and subsequent ketalization with neopentyl glycol (IV) using p-TsOH·H2O and, optionally, H2SO4 in MeCN gives monoprotected ketoaldehyde (V) (1). Finally, cyclization of ketoaldehyde derivative (V) with 4-aminobenzenesulfonamide (VI) in the presence of AcOH in PrOH/H2O at 90-100 °C furnishes apricoxib (1, 2).
Intermediate (V) can also be prepared by reaction of 1-(4-ethoxyphenyl)-2-buten-1-one (VII) with CH3NO2 in the presence of DBU in THF to produce nitro ketone (VIII). Subsequent treatment of nitro derivative (VIII) with neopentyl glycol (IV) and NaOMe and MeOH gives acetal (V) (2).
In an alternative strategy, condensation of 4-ethoxyacetaldehyde (IX) with 4-sulfamoylaniline (VI) in refluxing EtOH furnishes N-(4-ethoxybenzylidene)-4-sulfamoylaniline (X), which then condenses with trimethylsilyl cyanide (XI) in the presence of ZnCl2 in THF yielding α-amino nitrile (XII). Cyclization of this compound with methacrolein (XIII) using LiHMDS in THF affords apricoxib (3). Scheme 1.

参考文献中间体

合成目标

【1】 Kojima, S., Ooyama, J. (Daiichi Sankyo Co., Ltd.). Process for production of brominated acetophenone. WO 2008020617.
【2】 Fujimoto, K., Takebayashi, T., Noguchi, Y., Saitou, T. (Daiichi Sankyo Co., Ltd.). Production of 4-methyl-1,2-diarylpyrrole and intermediate for synthesizing the same. JP 2000080078.
【3】 Kimura, T., Noguchi, Y., Nakao, A., Suzuki, K., Ushiyama, S., Kawara, A., Miyamoto, M. (Daiichi Sankyo Co., Ltd.). 1,2-Diphenylpyrrole derivatives, their preparation and their therapeutic uses. CA 2201812, EP 0799823, JP 1997823971, US 5908858.

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)	66028	4'-Ethoxyacetophenone; 1-(4-Ethoxyphenyl)ethan-1-one	1676-63-7	C₁₀H₁₂O₂	详情	详情
(II)	66029	2-Bromo-1-(4-Ethoxyphenyl)Ethanone; Zinc02649911	51012-63-6	C₁₀H₁₁BrO₂	详情	详情
(III)	66030	2-methyl-N-(2-methylpropyl)-N-prop-1-enylpropan-1-amine	100334-82-5	C₁₁H₂₃N	详情	详情
(IV)	12641	Neopentyl glycol; 2,2-Dimethyl-1,3-propanediol	126-30-7	C₅H₁₂O₂	详情	详情
(V)	66031			C₁₈H₂₆O₄	详情	详情
(VI)	54719	4-Aminobenzenesulfonamide; p-Aminobenzene sulfonyl amide; p-Aminobenzenesulfonamide; p-Anilinesulfonamide; Sulfanilamide	63-74-1	C₆H₈N₂O₂S	详情	详情
(VII)	66032			C₁₂H₁₄O₂	详情	详情
(VIII)	66033			C₁₃H₁₇NO₄	详情	详情
(IX)	66034	4-Ethoxybenzaldehyde; p-Ethoxybenzaldehyde	10031-82-0	C₉H₁₀O₂	详情	详情
(X)	66035			C₁₅H₁₆N₂O₃S	详情	详情
(XI)	61447	Trimethylsilyl cyanide; Cyanotrimethylsilane; TMSCN; Trimethylsilyl carbonitrile; Trimethylsilylnitrile; Cyantrimethylsilan; Trimethylsilylnitrile; Cyanotrimethylsilane; TRIMETHYLSILYLCYANIDE; Cyanotrimethylsilane; (CYANOTRIMETHYLSILANE)	7677-24-9	C₄H₉NSi	详情	详情
(XII)	66036			C₁₆H₁₇N₂O₃S	详情	详情
(XIII)	11387	2-Methylacrylaldehyde; Methacrylaldehyde	78-85-3	C₄H₆O	详情	详情

Extended Information