SB-215505

6-氯-2,3-二氢-5-甲基-N-5-喹啉基-1H-吲哚-1-甲酰胺Chemical Name: 6-Chloro-5-methyl-N-(5-quinolinyl)-2,3-dihydro-1H-indole-1-carboxamide
CAS No. 162100-15-4
项目整合开发状态: Preclinical
项目研究机构: GlaxoSmithKline (Originator)
合成路线:The heating of nicotinoyl azide (I) in refluxing toluene gives the corresponding isocyanate (II),which without isolation is condensed with 6-chloro-5-(methylsulfanyl)indoline (IV) to afford the target compound.Intermediate indoline (IV) is obtained by reduction of 6-chloro-5-(methylsulfanyl)indole (III) with NaBH3CN in HOAc.

合成路线:Alkylation of 3-chloro-4-methylaniline (I) with bromoacetaldehyde diethyl acetal (II) afforded secondary amine (III).Subsequent cyclization of (III) in boiling trifluoroacetic acid/trifluoroacetic anhydride provided a (3:2) mixture of indoles (IV) and (V),from which the desired 6-chloro isomer (IV) was isolated by column chromatography,and then reduced to indoline (VI) using NaBH3CN in AcOH.5-Aminoquinoline (VII) was treated with carbonyl diimidazole to give intermediate (VIII).This was finally coupled with indoline (VI) in DMF at 100 C to yield the corresponding urea.