N-(4-sulfanylphenyl)acetamide -Drug Synthesis Database

【结构式】

【分子编号】34329

【品名】N-(4-sulfanylphenyl)acetamide

【CA登记号】1126-81-4

【分子式】C₈H₉NOS

【分子量】167.2316

【元素组成】C 57.46% H 5.42% N 8.38% O 9.57% S 19.17%

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：(V)

Coupling of (IV) in a nitrogen atmosphere with 4-acetamidothiophenol (V) in refluxing acetone in the presence of K2CO3 affords cis-N-[4-[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-ylmethylthio]phenyl]acetamide, which is deacylated with NaOH in refluxing i-PrOH to give cis-4-[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl-methyl)-1,3-dioxolan-4-ylmethylthio]benzenamine (VII). This compound is converted with ethylchloroformate (II) into the title compound which is isolated as the monohydrochloride on treatment with i-PrOH / HCl.

参考文献中间体

合成目标

【1】 Heeres, J.; Van der Veken, L.J.E.; Novel (2-aryl-4-phenylthioalkyl-1,3-dioxolan-2-yl-methyl)azole derivatives. DE 3166517D; EP 0052905 .
【2】 Van Ginckel, R.; Geuens, G.; Heeres, J.; Tubulozole Hydrochloride. Drugs Fut 1984, 9, 12, 911.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	11229	1-[(Chlorocarbonyl)oxy]ethane;ethyl carbonochloridate; Carbonchloridic acid ethyl ester;Ethyl chloroformate;Ethyl chlorocarbonate	541-41-3	C₃H₅ClO₂	详情	详情
(IV)	34328	1-[[(2S,4S)-2-(2,4-dichlorophenyl)-4-([[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]methyl)-1,3-dioxolan-2-yl]methyl]-1H-imidazole		C₁₇H₂₀Cl₂N₂O₃S	详情	详情
(V)	34329	N-(4-sulfanylphenyl)acetamide	1126-81-4	C₈H₉NOS	详情	详情
(VI)	34330	N-[4-([[(2S,4S)-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methyl]sulfanyl)phenyl]acetamide		C₂₂H₂₁Cl₂N₃O₃S	详情	详情
(VII)	34331	4-([[(2S,4S)-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methyl]sulfanyl)aniline; 4-([[(2S,4S)-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methyl]sulfanyl)phenylamine		C₂₀H₁₉Cl₂N₃O₂S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The condensation between 4-(acetylamino)thiophenol (I) and 5-chloro-2-nitroaniline (II) produced the diaryl sulfide (III). Nitro group reduction in (III) employing SnCl2 gave the phenylenediamine (IV), which was cyclized to the benzimidazole (VI) upon treatment with N,N'-bis(methoxycarbonyl)-S-methylisothiourea (V). Hydrolysis of the acetamido group of (VI) with HCl in MeOH afforded aniline (VII). This was acylated with N-Boc-alanine (VIII) in the presence of EDC to yield amide (IX). The N-Boc protecting group of (IX) was finally removed by treatment with trifluoroacetic acid.

参考文献中间体

合成目标

【1】 Lewis, G.S.; Nolan, J.; Davis, P.D.; Naylor, M.A.; Thomson, P.; Hill, S.A.; Benzimidazole carbamates: A new structural class of vascular targeting agents. Proc Amer Assoc Cancer Res 2001, 42, Abst 2000.
【2】 Davis, P.D. (Angiogene Pharmaceuticals Ltd.); Benzimidazole vascular damaging agents. EP 1140078; WO 0041669 .

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)	34329	N-(4-sulfanylphenyl)acetamide	1126-81-4	C₈H₉NOS	详情	详情
(II)	15709	5-chloro-2-nitrophenylamine; 5-chloro-2-nitroaniline	1635-61-6	C₆H₅ClN₂O₂	详情	详情
(III)	51869	N-[4-[(3-amino-4-nitrophenyl)sulfanyl]phenyl]acetamide		C₁₄H₁₃N₃O₃S	详情	详情
(IV)	51870	N-[4-[(3,4-diaminophenyl)sulfanyl]phenyl]acetamide		C₁₄H₁₅N₃OS	详情	详情
(V)	28696	methyl (Z)-[(methoxycarbonyl)amino](methylsulfanyl)methylidenecarbamate		C₆H₁₀N₂O₄S	详情	详情
(VI)	51871	methyl 5-[[4-(acetamido)phenyl]sulfanyl]-1H-benzimidazol-2-ylcarbamate		C₁₇H₁₆N₄O₃S	详情	详情
(VII)	51872	methyl 5-[(4-aminophenyl)sulfanyl]-1H-benzimidazol-2-ylcarbamate		C₁₅H₁₄N₄O₂S	详情	详情
(VIII)	26450	Boc-L-Alanine;(S)-2-((tert-butoxycarbonyl)amino)propanoic acid;N-Boc-L-alanine; (2S)-2-[(tert-butoxycarbonyl)amino]propionic acid	15761-38-3	C₈H₁₅NO₄	详情	详情
(IX)	51873	methyl 5-[[4-([(2S)-2-[(tert-butoxycarbonyl)amino]propanoyl]amino)phenyl]sulfanyl]-1H-benzimidazol-2-ylcarbamate		C₂₃H₂₇N₅O₅S	详情	详情

Extended Information