1,3-benzodioxole-5-carbonyl chloride -Drug Synthesis Database

【结构式】

【分子编号】28821

【品名】1,3-benzodioxole-5-carbonyl chloride

【CA登记号】20850-43-5

【分子式】C₈H₅ClO₃

【分子量】184.5786

【元素组成】C 52.06% H 2.73% Cl 19.21% O 26%

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：(LIV)

The cyclization of 3,4,5-trimethoxycinnamic acid ethyl ester (LI) with malonic acid ethyl ester potassium salt (LII) by means of Mn(OAc)3 gives the tetrahydrofuranone (LIII), which is acylated with 1,3-benzodioxol-5-ylcarbonyl chloride (LIV) yielding the tetrahydrofuranone (LV). Finally, this compound is rearranged and decarboxylated with SnCl4 to the target intermediate (XI).

参考文献中间体

合成目标

【1】 Ward, R.S.; Synthesis of podophyllotoxin and related compounds. Synthesis 1992, 719.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XI)	34966	ethyl (5R,6R)-8-oxo-5-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydronaphtho[2,3-d][1,3]dioxole-6-carboxylate		C₂₃H₂₄O₈	详情	详情
(LI)	35003	ethyl (E)-3-(3,4,5-trimethoxyphenyl)-2-propenoate		C₁₄H₁₈O₅	详情	详情
(LII)	35004	potassium 3-methoxy-3-oxopropanoate	38330-80-2	C₄H₅KO₄	详情	详情
(LIII)	35005	4-ethyl 3-methyl (3S,4R,5R)-2-oxo-5-(3,4,5-trimethoxyphenyl)tetrahydro-3,4-furandicarboxylate		C₁₈H₂₂O₉	详情	详情
(LIV)	28821	1,3-benzodioxole-5-carbonyl chloride	20850-43-5	C₈H₅ClO₃	详情	详情
(LV)	35006	4-ethyl 3-methyl (3S,4R,5R)-3-(1,3-benzodioxol-5-ylcarbonyl)-2-oxo-5-(3,4,5-trimethoxyphenyl)tetrahydro-3,4-furandicarboxylate		C₂₆H₂₆O₁₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The acylation of 3',5'-di-O-(chloroacetyl)-5-fluoro-2'-deoxyuridine (I) with 3,4-methylenedioxybenzoyl chloride (II) by means of triethylamine in dichloromethane gives 3',5'-di-O-(chloroacetyl)-3-(3,4-methylenedioxybenzoyl)-2'-deoxy-5-fluorouridine (III), which is then hydrolyzed with triethylamine in methanol-THF.

参考文献中间体

合成目标

【1】 Terashima, N.; Kitayama, I.; Yamaguchi, T.; Hiraiwa, T.; Omori, M.; Senoura, M.; Yotsuji, M.; Kodama, T.; Kodama, Y.; Aoyama, H. (Toyama Chemical Co., Ltd.); 5-Fluoro-(beta-uridine or 2'-deoxy-beta-uridine) derivatives, a process for producing the same and a carcinostatic agent containing the same. DE 2923368 .
【2】 Castaner, J.; Castaner, R.M.; Hoshi, A.; Serradell, M.N.; TK-117. Drugs Fut 1987, 12, 9, 865.

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)	28820	[(2R,3S,5R)-3-[(2-chloroacetyl)oxy]-5-[5-fluoro-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl]methyl 2-chloroacetate		C₁₃H₁₃Cl₂FN₂O₇	详情	详情
(II)	28821	1,3-benzodioxole-5-carbonyl chloride	20850-43-5	C₈H₅ClO₃	详情	详情
(III)	28822	(2R,3S,5R)-5-[3-(1,3-benzodioxol-5-ylcarbonyl)-5-fluoro-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-2-[[(2-chloroacetyl)oxy]methyl]tetrahydro-3-furanyl 2-chloroacetate		C₂₁H₁₇Cl₂FN₂O₁₀	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

Reaction of piperonyloyl chloride (I) with N,O-dimethylhydroxylamine gives rise to the Weinreb amide (II). This is then condensed with the lithium anion of 2-picoline (III) to produce ketone (IV). Nitrosation of (IV) with NaNO2/HCl leads to keto oxime (V). Subsequent cyclization of (V) with p-formylbenzonitrile (VI) in the presence of ammonium acetate in AcOH affords the N-hydroxy imidazole (VII), which is further reduced to the triaryl imidazole (VIII) by means of triethyl phosphite in DMF. The cyano group of (VIII) is then hydrolyzed under acidic conditions to provide carboxylic acid (IX). After activation of (IX) as the corresponding acid chloride (X), treatment with ammonium hydroxide in THF yields the target carboxamide (1,2).

参考文献中间体

合成目标

【1】 Callahan, J.F.; Burgess, J.L.; Fornwald, J.A.; Gaster, L.M.; Harling, J.D.; Harrington, F.P.; Heer, J.; Kwon, C.; Lehr, R.; Mathur, A.; Olson, B.A.; Weinstock, J.; Laping, N.J.; Identification of novel inhibitors of the transforming growth factor beta1 (TGF-beta1) type 1 receptor (ALK5). J Med Chem 2002, 45, 5, 999.
【2】 Callahan, J.F.; Burgess, J.L. (GlaxoSmithKline Inc.); Triarylimidazoles. EP 1169317; JP 2002541253; US 6465493; WO 0061576 .

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)	28821	1,3-benzodioxole-5-carbonyl chloride	20850-43-5	C₈H₅ClO₃	详情	详情
(II)	64530	N-methoxy-N-methyl-1,3-benzodioxole-5-carboxamide		C₁₀H₁₁NO₄	详情	详情
(III)	17590	2-methylpyridine; 2-picoline	109-06-8	C₆H₇N	详情	详情
(IV)	64531	1-(1,3-benzodioxol-5-yl)-2-(2-pyridinyl)-1-ethanone		C₁₄H₁₁NO₃	详情	详情
(V)	64532	1-(1,3-benzodioxol-5-yl)-2-(2-pyridinyl)-1,2-ethanedione 2-oxime		C₁₄H₁₀N₂O₄	详情	详情
(VI)	17552	4-formylbenzonitrile; 4-Cyanobenzaldehyde	105-07-7	C₈H₅NO	详情	详情
(VII)	64533	4-[4-(1,3-benzodioxol-5-yl)-1-hydroxy-5-(2-pyridinyl)-1H-imidazol-2-yl]benzonitrile		C₂₂H₁₄N₄O₃	详情	详情
(VIII)	64534	4-[4-(1,3-benzodioxol-5-yl)-5-(2-pyridinyl)-1H-imidazol-2-yl]benzonitrile		C₂₂H₁₄N₄O₂	详情	详情
(IX)	64535	4-[4-(1,3-benzodioxol-5-yl)-5-(2-pyridinyl)-1H-imidazol-2-yl]benzoic acid		C₂₂H₁₅N₃O₄	详情	详情
(X)	64536	4-[4-(1,3-benzodioxol-5-yl)-5-(2-pyridinyl)-1H-imidazol-2-yl]benzoyl chloride		C₂₂H₁₄ClN₃O₃	详情	详情

Extended Information