SDZ-87-469, -Drug Synthesis Database

【结构式】

【药物名称】SDZ-87-469

【化学名称】(E)-3-Chloro-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methylbenzo[b]thiophene-7-methanamine hydrochloride

【CA登记号】87906-33-0, 87906-31-8 (free base), 87906-32-9 (Z-isomer;free base)

【分子式】C₁₉H₂₃Cl₂NS

【分子量】368.37186

【开发单位】Novartis (Originator)

【药理作用】Antifungal Agents, ANTIINFECTIVE THERAPY

合成路线1

A new synthesis of SDZ-87469 has been published: The chlorination of 7-methylbenzo[b]thiophene (I) gives 2,3-dichloro-7-methylbenzo[b]thiophene (II), which is selectively dechlorinated with butyllithium and hydrolysis, yielding 3-chloro-7-methylbenzo[b]thiophene (III). The bromination of (III) with N-bromosuccinimide (NBS) in DMF affords 7-(bromomethyl)-3-chlorobenzo[b]thiophene (IV), which is finally condensed with N,6,6-trimethylhep-2-en-4-yn-1-amine (V) (E + Z mixture) by means of K2CO3 in DMF. The pure E-isomer is obtained by crystallization of the E + Z mixture of the hydrochlorides in ethanol. Amine (V) is obtained by reaction of the corresponding bromo derivative (IV) with methylamine.

参考文献中间体

【1】 Petranyi, G.; Stutz, A.; J Med Chem 1984, 27, 12, 1539-43.
【2】 Stutz, A.; Nussbaumer, P.; Rev Iberoam Micol 1988, 5, 1, 89.
【3】 Loozen, H.; Godefroi, E.; J Org Chem 1973, 38, 5, 1056-7.
【4】 Stutz, A. (Novartis Deutschland GmbH); New allylamines and their use.. DE 3302814 .
【5】 Nussbaumer, P.; Petranyi, G.; Stutz, A.; Synthesis and structure-activity relationships of benzo[b]thienylallylamine antimycotics. J Med Chem 1991, 34, 1, 65-73.

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)	12835	7-Methyl-1-benzothiophene		C₉H₈S	详情	详情
(II)	12836	2,3-Dichloro-7-methyl-1-benzothiophene		C₉H₆Cl₂S	详情	详情
(III)	12837	3-Chloro-7-methyl-1-benzothiophene		C₉H₇ClS	详情	详情
(IV)	12838	7-(Bromomethyl)-3-chloro-1-benzothiophene		C₉H₆BrClS	详情	详情
(V)	12839	N-[(E)-6,6-Dimethyl-2-hepten-4-ynyl]-N-methylamine; (E)-N,6,6-Trimethyl-2-hepten-4-yn-1-amine		C₁₀H₁₇N	详情	详情
(VI)	10109	(E)-1-Bromo-6,6-dimethyl-2-hepten-4-yne	78629-21-7	C₉H₁₃Br	详情	详情

Extended Information