SR-149415, SSR-149415

Chemical Name: (-)-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
CAS No. 352276-92-7, 352277-03-3 (diastereomer), 352277-05-5 (diastereomer)
项目整合开发状态: Phase I
项目研究机构: Sanofi-Aventis (Originator)
合成路线: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).

合成路线: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.