The starting material of the scheme
is 2,3-dibromo-5-chloropyridine (15). It goes through five different steps in
order to get the desired intermediate C of the chloro variant (21). The
starting material provides a C-3 aldehyde which is then reacted with DMF in
order to get its corresponding alcohol (16). Following its protection with a
THP group, a second selective transmetalation occurs using iPrMgCl in toluene along with the addition of DMF. This results in
an anion that corresponds with C-2 aldehyde (17). This aldehyde is condensed
with N-tert-butyl azaindolene (18) in
order to produce its Z-isomer (19). The Z-isomer (19), a highly crystalline
alkene, is reduced with NaBH4 followed by THP deprotection, producing the primary alcohol (20). In order to produce the desired
intermediate (21), this primary alcohol (20) is chlorinated using SOCl 2 in the
presence of DMF.