Nitrosation of tetrahydrobenzothiazepine (I) with NaNO2 and HOAc, followed by LiAlH4 reduction of the resulting N-nitroso derivative (II), furnished hydrazine (III). Subsequent Fischer indole cyclization of hydrazine (III) with piperidone hydrate (IV) under acidic conditions afforded the tetracyclic system (V). The pyrrole ring double bond of (V) was then reduced employing NaBH3CN and CF3COOH to provide the racemic cis-tetracycle (VI). Resolution of (VI) was carried out by preparative chiral HPLC of the corresponding N-Boc derivative. The desired N-Boc enantiomer (VII) was then deprotected by acidic treatment to give the chiral secondary amine (VIII). This was finally alkylated with 4-chloro-4'-fluorobutyrophenone (IX) to yield the title compound.

Nitrosation of dihydrobenzoxazine (I) with NaNO2 and HOAc, followed by LiAlH4 reduction of the resulting N-nitroso derivative (II), furnished hydrazine (III). Subsequent Fischer indole cyclization of hydrazine (III) with piperidone hydrate (IV) under acidic conditions afforded the tetracyclic system (V). The pyrrole ring double bond of (V) was then reduced employing NaBH3CN and CF3COOH to provide the racemic cis-tetracycle (VI). Resolution of (VI) was carried out by preparative chiral HPLC of the corresponding N-Boc derivative. The desired N-Boc enantiomer (VII) was then deprotected by acidic treatment to give the chiral secondary amine (VIII). This was finally alkylated with 2'-amino-4-chloro-4'-fluorobutyrophenone (IX) to yield the title compound.