SR-149415, SSR-149415, -Drug Synthesis Database

【结构式】

【药物名称】SR-149415, SSR-149415

【化学名称】(-)-1-[5-Chloro-1-(2,4-dimethoxyphenylsulfonyl)-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4(R)-hydroxy-L-proline N,N-dimethylamide

【CA登记号】352276-92-7, 352277-03-3 (diastereomer), 352277-05-5 (diastereomer)

【分子式】C₃₀H₃₂ClN₃O₈S

【分子量】630.12184

【开发单位】Sanofi-synthélabo (Originator)

【药理作用】Antidepressants, Anxiolytics, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS, Vasopressin V1b Antagonists

合成路线1 合成路线2

合成路线1

Addition of 2-methoxyphenylmagnesium bromide (II) to 5-chloroisatin (I) provided the carbinol adduct (III). Chlorination of (III) using SOCl2 in the presence of pyridine gave chloride (IV).

参考文献中间体

【1】 Wagnon, J.; Tonnerre, B.; Roux, R.; Serradeil-Le Gal, C. (Sanofi-Synthelabo); Novel 1,3-dihydro-2H-indol-2-one derivs., preparation method and pharmaceutical compsns. containing them. EP 1255751; FR 2804114; WO 0155130 .

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)	14099	5-Chloro-1H-indole-2,3-dione; 5-Chloroisatin	17630-76-1	C₈H₄ClNO₂	详情	详情
(II)	19704	bromo(2-methoxyphenyl)magnesium		C₇H₇BrMgO	详情	详情
(III)	56072	5-chloro-3-hydroxy-3-(2-methoxyphenyl)-1,3-dihydro-2H-indol-2-one		C₁₅H₁₂ClNO₃	详情	详情
(IV)	56073	3,5-dichloro-3-(2-methoxyphenyl)-1,3-dihydro-2H-indol-2-one		C₁₅H₁₁Cl₂NO₂	详情	详情

合成路线2

Condensation of N-Boc-4-hydroxyproline (V) with dimethylamine using BOP as the coupling reagent furnished amide (VI). The N-Boc protecting group of (VI) was then removed under acidic conditions to yield prolinaminde (VII). Alkylation of (VII) with the chloro oxindole (IV) produced the N-indolyl proline derivative (VIII) as a mixture of diastereoisomers, separable by column chromatography. Finally, indole N acylation in (VIII) by means of 2,4-dimethoxybenzenesulfonyl chloride (IX) in the presence of NaH furnished the target sulfonamide.

参考文献中间体

【1】 Wagnon, J.; Tonnerre, B.; Roux, R.; Serradeil-Le Gal, C. (Sanofi-Synthelabo); Novel 1,3-dihydro-2H-indol-2-one derivs., preparation method and pharmaceutical compsns. containing them. EP 1255751; FR 2804114; WO 0155130 .

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)	56073	3,5-dichloro-3-(2-methoxyphenyl)-1,3-dihydro-2H-indol-2-one		C₁₅H₁₁Cl₂NO₂	详情	详情
(V)	16094	(2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid;1-(tert-butoxycarbonyl)-4®-hydroxy-L-proline;(2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxytetrahydro-1H-pyrrole-2-carboxylic acid	16094	C₁₀H₁₇NO₅	详情	详情
(VI)	56074	tert-butyl (2S,4R)-2-[(dimethylamino)carbonyl]-4-hydroxy-1-pyrrolidinecarboxylate		C₁₂H₂₂N₂O₄	详情	详情
(VII)	56075	(2S,4R)-4-hydroxy-N,N-dimethyl-2-pyrrolidinecarboxamide		C₇H₁₄N₂O₂	详情	详情
(VIII)	56076	(2S,4R)-1-[5-chloro-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-hydroxy-N,N-dimethyl-2-pyrrolidinecarboxamide		C₂₂H₂₄ClN₃O₄	详情	详情
(IX)	56077	2,4-dimethoxybenzenesulfonyl chloride		C₈H₉ClO₄S	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)