methyl 5-methoxy-2-sulfanylbenzoate -Drug Synthesis Database

【结构式】

【分子编号】13887

【品名】methyl 5-methoxy-2-sulfanylbenzoate

【CA登记号】

【分子式】C₉H₁₀O₃S

【分子量】198.2426

【元素组成】C 54.53% H 5.08% O 24.21% S 16.18%

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：(I)

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：(V)

Treatment of 2,5-dihydroxybenzoic acid (I) with dimethyl sulfate and K2CO3 afforded methyl 2-hydroxy-5-methoxybenzoate (II). Condensation of (II) with dimethylthiocarbamoyl chloride gave the O-aryl thiocarbamate (III), which underwent thermal rearrangement to the S-aryl isomer (IV) upon heating at 265 C in diphenyl ether. Subsequent hydrolysis of the thiocarbamate group of (IV) furnished the desired thiophenol compound (V). Cyclization of the mercapto ester (V) with 2-chloroethylamine (VI) gave rise to the benzothiazepinone (VII), which was further reduced to the benzothiazepine (VIII) using LiAlH4. Acylation of (VIII) with acryloyl chloride (IX) provided the acrylamide (X). Finally, Michael addition of 4-benzylpiperidine (XI) to acrylamide (X) yielded the title compound.

参考文献中间体

合成目标

【1】 Kaneko, N.; Oosawa, T.; Sakai, T.; Oota, H. (Kirin Brewery Co., Ltd.); 1,4-Benzothiazepine derivs.. EP 0565721; US 5416066; WO 9212148 .

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)	60415	2,5-dihydroxybenzoic acid		C₇H₆O₄	详情	详情
(II)	60416	methyl 2-hydroxy-5-methoxybenzoate		C₉H₁₀O₄	详情	详情
(III)	60417	methyl 2-{[(dimethylamino)carbothioyl]oxy}-5-methoxybenzoate		C₁₂H₁₅NO₄S	详情	详情
(IV)	60418	methyl 2-{[(dimethylamino)carbonyl]sulfanyl}-5-methoxybenzoate		C₁₂H₁₅NO₄S	详情	详情
(V)	13887	methyl 5-methoxy-2-sulfanylbenzoate		C₉H₁₀O₃S	详情	详情
(VI)	33455	2-chloro-1-ethanamine; 2-chloroethylamine		C₂H₆ClN	详情	详情
(VII)	60419	7-methoxy-3,4-dihydro-1,4-benzothiazepin-5(2H)-one		C₁₀H₁₁NO₂S	详情	详情
(VIII)	60420	7-methoxy-2,3,4,5-tetrahydro-1,4-benzothiazepine; methyl 2,3,4,5-tetrahydro-1,4-benzothiazepin-7-yl ether		C₁₀H₁₃NOS	详情	详情
(IX)	11577	Acryloyl chloride; Acrylyl chloride;2-Propenoyl chloride	814-68-6	C₃H₃ClO	详情	详情
(X)	60421	1-[7-methoxy-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl]-2-propen-1-one		C₁₃H₁₅NO₂S	详情	详情
(XI)	26225	4-benzylpiperidine	31252-42-3	C₁₂H₁₇N	详情	详情

Extended Information