Process for preparing Tadalafil and its intermediate
AssigneeAlembic Limited
InventorsPandurang Balwant Deshpande, Bharat Becharbhai Boda, Sachin Surendra Surti, Pranay Pravinchandra Shah
Life of this patent
Estimating the term…
Abstract
The present invention relates an improved process for the preparation of tetrahydro-β-carboline derivative of formula (V) which is useful as an intermediate for the preparation of Tadalafil of formula (I). Moreover, the present invention relates to the process for the preparation of Tadalafil of formula (I)
Claims11
A process for the preparation of Tadalafil comprising a step of reacting an acid addition salt of D-Tryptophan methyl ester of formula (IIIa)
- with piperonal of formula (IV)
- in the presence of high boiling solvent wherein high boiling solvent is selected from N,N-Dimethyl acetamide, Dimethyl sulfoxide, N,N-dimethyl formamide, N-methyl pyrrolidine or mixture thereof and in the presence of dehydrating agent to obtain compound of formula (V)
A process for the preparation of Tadalafil comprising a step of reacting D-Tryptophan methyl ester hydrochloride of formula (III)
- with piperonal of formula (IV)
- in the presence of dehydrating agent and high boiling solvent wherein high boiling solvent is selected from N,N-Dimethyl acetamide, Dimethyl sulfoxide, N,N-dimethyl formamide, N-methyl pyrrolidine or mixture thereof to obtain compound of formula (V)
- as mixture of cis and trans isomer which is reacted further without isolating and separating isomers with an aqueous HCl to provide hydrochloride salt of cis isomer of compound of formula (V) as major isomer.
A process of preparation of Tadalafil comprising steps of
- (i) reacting D-Tryptophan methyl ester hydrochloride of formula (III)
- with piperonal of formula (IV)
- in the presence of dehydrating agent and high boiling solvent wherein high boiling solvent is selected from N,N-Dimethyl acetamide, Dimethyl sulfoxide, N,N-dimethyl formamide, N-methyl pyrrolidine or mixture thereof to obtain compound of formula (V)
- as mixture of cis and trans isomer which is reacted further without isolating and separating isomers with an aqueous HCl to provide hydrochloride salt of cis isomer of compound of formula (V) as major isomer
- (ii) reacting the compound of formula (V) obtained hereinabove step with chloroacetyl chloride in the presence of base and an organic solvent to get intermediate of formula (VI)
- which is further reacted with aqueous methylamine solution to obtain Tadalafil of formula (I)
Dependencies are inferred from the claim text.