(2,4-Dichlorophenyl)hydrazine monohydrochloride → Methyl N-(4-{1-[(4-chlorophenyl)(5,7-dichloro-1H-indol-3-yl)methyl]butyl}benzoyl)-beta-alaninate

Participants

Reaction Conditions

Reaction Steps

An acetic acid solution (5 ml) containing the intermediate from Step B (200 mg, 0.47 mmol), 2,4-dichlorophenyl hydrazine hydrochloride (120 mg, 0.56 mmol) and ZnCl2 (2.29M in AcOH, 0.61 ml, 1.4 mmol) was heated at 80° C. for 30 minutes. The solution was concentrated and the residue dissolved in EtOAc. The EtOAc solution was washed with water, brine and dried over Na2SO4. The filtered solution was concentrated and the residue purified by silica gel chromatography using a hexanes/EtOAc gradient to give the title compound as a mixture of diastereomers. The mixture was purified further using reverse phase HPLC. The major (and more active) diastereomer, which is also the slower (second) eluting on HPLC, was resolved on a Chiralpak AD-H column (2 cm×25 cm) eluting with 10% EtOH/Heptane at 9 ml/min.

Provenance & Evidence