The synthesis is highlighted in the Scheme.
Bromoacetaldehyde dimethyl acetal (44) was condensed with
methylamine with KOH in refluxing ethyleneglycol for 3 hr
to give 33% yield of bis(2,2-dimethoxyethyl)amine (45),
which was cyclized with acetonedicarboxylic acid (46) and
methylamine to generate 3,9-dimethyl-3,9-diazabicyclo-
[3.3.1]nonan-7-one (47) in 12% yield. Compound 47 was
reacted with hydroxylamine in refluxing pyridine and ethanol
mixture to give corresponding oxime 48 in 88% yield,
which was subsequently reduced with hydrogen over Raney
Ni in hot ethanol in the presence of ammonium acetate at 50
kg/cm2 to give amine 49 in 89% yield. Compound 49 was condensed with 1H-indazole-3-carbonyl chloride (50) in
pyridine with catalytic amount of DMAP to give crude
indisteron free base, which was re-crystallized from
chloroform/hexane to give indisteron free base as colorless
crystals in 16% yield. Finally, the free base was treated with
hydrogen chloride to give indisteron hydrochloride (VII).
