CI-959, -Drug Synthesis Database

【结构式】

【药物名称】CI-959

【化学名称】3-Isopropoxy-5-methoxy-N-(1H-tetrazol-5-yl)benzo[b]thiophene-2-carboxamide sodium salt

【CA登记号】104795-68-8, 104795-66-6 (free acid)

【分子式】C₁₄H₁₄N₅NaO₃S

【分子量】355.35318

【开发单位】Pfizer (Originator)

【药理作用】Antiallergy/Antiasthmatic Drugs, Asthma Therapy, RESPIRATORY DRUGS, Mediator Release Inhibitors

合成路线1 合成路线2

合成路线1

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

【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

Saponification of ester (IV) yields the alkoxycarboxylic acid (VII), which is coupled with 5-aminotetrazole in the presence of 1,1'-carbonylbis(1H-imidazole) (CDI) to provide the carboxamidotetrazole (VIII). Reaction of (VIII) with sodium hydroxide furnishes CI-959 (IX) as the tetrazole sodium salt.

参考文献中间体

【1】 Connor, D.T.; Cetenko, W.A.; Mullican, M.D.; Novel benzothiophene-, benzofuran-, and naphthalenecarboxamidotetrazoles as potential antiallergy agents. J Med Chem 1992, 35, 5, 958-65.
【2】 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	分子式	供应商	用于合成
(IV)	13890	methyl 3-isopropoxy-5-methoxy-1-benzothiophene-2-carboxylate	C₁₄H₁₆O₄S	详情	详情
(VII)	13893	3-Isopropoxy-5-methoxy-1-benzothiophene-2-carboxylic acid	C₁₃H₁₄O₄S	详情	详情
(VIII)	13894	3-Isopropoxy-5-methoxy-N-(1H-1,2,3,4-tetraazol-5-yl)-1-benzothiophene-2-carboxamide	C₁₄H₁₅N₅O₃S	详情	详情

Extended Information