LY-367265

Chemical Name: 1-[2-[4-(6-Fluoro-1H-indol-3-yl)-1,2,3,6-tetrahydropyridin-4-yl]ethyl]-5,6-dihydro-1H,4H-[1,2,5]thiadiazolo[4,3,2-ij]quinoline 2,2-dioxide
CAS No. 210751-39-6, 210751-40-9 (phosphate (1:1) salt)
项目整合开发状态: Preclinical
项目研究机构: Lilly (Originator)
合成路线:The indole intermediate (V) has been obtained as follows: The reaction of 4-fluoro-2-nitrotoluene (I) with dimethylformamide dimethylacetal afforded enamine (II).Reductive cyclization of (II) by hydrogenation over Pd/C produced 6-fluoroindole (III).Subsequent condensation of indole (III) with piperidone monohydrate (IV) in the presence of KOH furnished the intermediate indolyl tetrahydropyridine (V).

合成路线:8-Amino-1,2,3,4-tetrahydroquinoline (VII) was obtained by catalytic hydrogenation of 8-nitroquinoline (VI) over PtO2.Condensation of (VII) with sulfamide in diglyme at 160 C gave rise to the tricyclic system (VIII),which was further alkylated with 1-bromo-2-chloroethane in the presence of NaH to yield chloride (IX).Finally,condensation between tetrahydropyridine (V) and chloride (IX) afforded the title compound.