3-Chloro-5-methoxy-1-benzothiophene-2-carbonyl chloride -Drug Synthesis Database

【结构式】

【分子编号】13892

【品名】3-Chloro-5-methoxy-1-benzothiophene-2-carbonyl chloride

【CA登记号】

【分子式】C₁₀H₆Cl₂O₂S

【分子量】261.12784

【元素组成】C 46% H 2.32% Cl 27.15% O 12.25% S 12.28%

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：(VI)

Alternate routes to the key benzo[b]thiophene ester intermediates (IV) are described: 1) Alkylation of the thiol ester (I) yields the diester (II), and a Dieckmann condensation of (II) with base provides the benzo[b]thiophene enol ester (III). Alkylation of (III) with 2-bromopropane then yields the ester intermediate (IV, R = CH3). 2) A shorter route to (IV) begins with cyclization of the cinnamic acid derivative (V) with thionyl choride (2) to give the chloro acid chloride (VI). Reaction of (VI) with the potassium salt of 2-propanol yields the ester (IV, R = CH(CH3)2).

参考文献中间体

合成目标

【1】 Higa, T.; Krubsack, A.J.; Oxidations by thionyl chloride. VI. Mechanism of the reaction with cinnamic acids. J Org Chem 1975, 40, 3037-45.
【2】 Johnson, J.; Tramondozzi; Bennet, O.F.; Synthesis of 2-methoxydibenzo[b,f][1,4]thiazapin-11(10H)-one 5,5-dioxide. Org Prep Proced Int 1974, 6, 287-93.
【3】 Unangst, P.C.; Connor, D.T.; Low, J.E.; Conroy, M.C.; CI-959. Drugs Fut 1994, 19, 1, 17.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV-1)	13890	methyl 3-isopropoxy-5-methoxy-1-benzothiophene-2-carboxylate		C₁₄H₁₆O₄S	详情	详情
(IV-2)	63809	isopropyl 3-isopropoxy-5-methoxy-1-benzothiophene-2-carboxylate		C₁₆H₂₀O₄S	详情	详情
(I)	13887	methyl 5-methoxy-2-sulfanylbenzoate		C₉H₁₀O₃S	详情	详情
(II)	13888	methyl 5-methoxy-2-[(2-methoxy-2-oxoethyl)sulfanyl]benzoate		C₁₂H₁₄O₅S	详情	详情
(III)	13889	methyl 3-hydroxy-5-methoxy-1-benzothiophene-2-carboxylate		C₁₁H₁₀O₄S	详情	详情
(V)	13891	(E)-3-(3-Methoxyphenyl)-2-propenoic acid; m-Methoxycinnamic acid	6099-04-3	C₁₀H₁₀O₃	详情	详情
(VI)	13892	3-Chloro-5-methoxy-1-benzothiophene-2-carbonyl chloride		C₁₀H₆Cl₂O₂S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Methyl 3-chloro-5-methoxybenzo[b]thiophene-2-carboxylate (II) was prepared from the known acid chloride (I) by treatment with methanol. Cyclization of the chloro ester (II) with cysteamine hydrochloride (III) in the presence of DBU afforded the target benzothienothiazepinone.

参考文献中间体

合成目标

【2】 Boschelli, D.H.; Connor, D.T.; Kramer, J.B.; Unangst, P.C. (Pfizer Inc.); Benzothiophene, benzofuran and indolethiazepinones, oxazepinones and diazepinones as inhibitors of cell adhesion and as inhibitors of HIV. EP 0749434; JP 1997509961; US 5489586; WO 9524408 .
【1】 Khatana, S.S.; et al.; Preparation of benzothieno[2,3-f]-1,4-oxazepin- and -thiazepin-5(2H)-ones and of benzothieno[3,2-e]-1,4-diazepin-5-ones. J Org Chem 1996, 61, 17, 6060.
【3】 Gracheck, S.J. (Pfizer Inc.); Use of thiazepine, oxazepine and diazepine cpds. for inhibiting HIV, herpesvirus and suppressing the immune system. EP 0817635; JP 1999502814; WO 9629077 .

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)	13892	3-Chloro-5-methoxy-1-benzothiophene-2-carbonyl chloride		C₁₀H₆Cl₂O₂S	详情	详情
(II)	51552	methyl 3-chloro-5-methoxy-1-benzothiophene-2-carboxylate		C₁₁H₉ClO₃S	详情	详情
(III)	13186	2-Aminoethanethiol; 2-Amino-1-ethanethiol; 2-Aminoethylhydrosulfide; Cysteamine	60-23-1	C₂H₇NS	详情	详情

Extended Information