Macor indole synthesis

Macor also exploited the Mori-Ban indole synthesis to synthesize several anti-migraine analogues of sumatriptan and homo-tiyptamines as potent and selective serotonin reuptake inhibitors (SSRIs). Noticeably, the presence of the second bromine (the bromine passenger ) on the substrate was not significantly deleterious to the reaction although a small amount of the 7-bromoindole might be sacrificed at the end of the reaction to consume the active palladium catalyst. The approach to 7-bromoindole could provide a general method to access 7-bromoindoles (a rare class of indole derivatives), which then could be further manipulated for the synthesis of more complex 7-substituted indoles. 

In synthesis of eletriptan (Relpax), Pfizer s triptan for the treatment of migraine, Macor again used the Mori—Ban indole synthesis as the key operation to assemble the indole ring. Jeffrey s conditions were once again employed to transform the o-bromo-A allylaniline into the indole core. 

The first outside group to use the M osza indole synthesis was Macor and colleagues [21-23]. A key feature of this chemistry is the use of a Mitsunobu reaction to functionalize the benzylnitrile as illustrated in Scheme 3 (equation 1) [21, 22]. Equation 2 presents Macor s synthesis of the... 

Scheme 3 Macor Applications of the Makosza Indole Synthesis...

Macor JE, Froman IT, Post RJ, Ryan K (1997) Synthesis and reactivity of pyrrolo[3,2-e]indole removal of a N-BOM group from an unactivated indole. Tetrahedron Lett 38 1673-1676... 

King HD, Meng Z, Denhart D, Mattson R, Kimura R, Wu D, Gao Q, Macor JE. Enantioselective synthesis of a highly potent selective serotonin reuptake inhibitor. An application of imidazolidinone catalysis to the alkylation of indoles with an a,(3-disubstituted a,(3-unsaturated aldehyde. Org. Lett. 2005 7(16) 3437-3440. 

---