FIELD OF INVENTION

The invention relates to a novel process for the preparation of (R)-5-(2-Aminopropyl)-2-methoxybenzenesulfonamide and its acid addition salts.
Formula I is a useful intermediate in the preparation of Tamsulosin.

BACKGROUND OF INVENTION

The compound 5-[2-[[2-(2-ethoxyphenoxy) ethyl] amino] propyl]-2-methoxy-benzenesulfonamide represented by the following structure.

Tamsulosin is a commercially marketed pharmaceutically active substance useful for the treatment of cardiac insufficiencies and benign prostatic hyperplasia. It is disclosed in EP34432 and US 4,731,478. The molecule, which will be further denoted as "Tamsulosin," has one asymmetric carbon (indicated by an asterisk in the above formula (1)), thus allowing for the existence of two enantiomers, conventionally denoted as (R)-or (S)-enantiomers. Both the free base and its acid addition salts may comprise either one or both of the two enantiomers. The single enantiomers have distinctive optical activity in polarized light and they also differ in their pharmaceutical activities. The commercially marketed product is the hydrochloride salt of the (R)-enantiomer of tamsulosin which is levorotary or (R) (-) tamsulosin hydrochloride.

The present invention discloses an efficient method for the preparation (R)-5-(2-Aminopropyl)-2-methoxybenzenesulfonamide of Formula I and its acid addition salts of Formula I.

Methods known in the art for compound of Formula II involves reducing the compound of Formula II with palladium/carbon catalyst at 4-5 atmosphere pressure.

OBJECTIVE OF THE INVENTION

An object of the present invention is to provide a process for the preparation {R)-5-(2-Aminopropyl)-2-methoxybenzenesulfonamide of Formula I.

and its acid addition salts using catalytic hydrogenation with milder conditions.

SUMMARY OF THE INVENTION

The instant invention discloses a Novel and efficient method for the preparation of (R)-5-(2-Aminopropyl)-2-methoxybenzenesulfonamide of the Formula I.

and its acid addition salts which comprises reducing the compound of Formula II

by catalytic hydrogenation in presence of ammonium formate.

DKTAILED DESCRIPTION OF THE INVENTTON

The present invention describes a novel process for the preparation of (i?)-5-(2-Aminopropyl)-2-methoxybenzenesulfonamide compound of Formula I from compound of formula II.

We have surprisingly found that the compound of Formula I can be prepared in good yield and high purity by catalytic hydrogenation of compound of formula II with various hydrogenating agents in presence of ammonium formate under milder reaction conditions.

The various hydrogenating agents may include Palladium on charcoal, Raney-Nickel, Platinum etc. Most preferably in Palladium on charcoal.

The catalytic hydrogenation of compound of formula II is effected in a suitable reaction media which includes alcohols like methanol, ethanol, isopropyl alcohol etc and more preferably methanol.

Optionally, the above catalytic hydrogenation is conducted in presence of additional hydrogen source like ammonium formate.

Normally, conventional hydrogenation procedure, although often offers selective reduction, it requires a special set of apparatus and is always associated with the usual risk of using hydrogen gas. However, in the present process of the invention this reaction is carried out with a hydrogenation source in presence of a metal catalyst such as Palladium, Raney nickel. Platinum etc.

The hydrogenation is conveniently effected at elevated temperatures. Most conveniently at reflux temperature of the reaction mixture. The reaction may be conveniently carried out by applying pressure or without applying pressure to the reaction vessel.

After completion of the reaction as monitored by TLC, the catalyst is removed by filtration and subsequently washed with methanol. The obtained filtrate, on evaporation under reduced pressure gives the crude compound which was further purified by slurring the reaction mass in acetone to give compound of formula I.

The compound of Formula I is isolated as its hydrochloride salt.

The compound obtained by the above process is characterized by spectroscopic methods. The compound of formula I is fiirther converted to Tamsulosin and its acid addition salts by methods known in the art.

The compound of Formula II is prepared by known methods in the art.

The following examples further illustrate the specific aspects of the present process and arc not intended to limit the scope thereof in any respect and should not be so construed.

EXAMPLE
PREPARATION OF (R)-5-(2-AMINOPROPYL)-2-METHOXYBENZENESULFONAMIDE
HYDROCHLORIDE:

The 2-methoxy-5-(R)-2-(l-phenylethylamino)propylbenzenesulfonamide HC1 (100 gms) is dissolved in methanol ( 2 Its) at 25-30 °C and stirred at ambient temperature for about 10 minutes. After complete dissolution, the ammonium formate (80 gms) is added to the reaction mixture followed by the addition of 5 % palladium (80 gms in 40 ml water) on charcoal in water at 25-30 °C. The reaction mixture was maintained for 2-3 hrs at 45-50 °C. After completion of the reaction, the reaction mass was filtered and washed with methanol. The obtained methanol organic layer was distilled out completely and acetone was charged to the residue. The slurry was cooled to 25-30 °C and later to 0-5 °C. After maintaining the slurry at 0-5 °C for 1 hr, the slurry was washed with acetone and filtered to obtain the title compound as off whit crystalline powder. Weight 70 gms MP : 264-269 °C.

CLAIMS

1) A process for the preparation of compound of formula I

and its acid addition salts which comprises reducing the compound of Formula II

by catalytic hydrogenation in presence of ammonium formate.

2) The process according to claim 1, wherein catalytic hydrogenation is performed employing hydrogenating catalysts like palladium, Raney Nikel, Platinum, more preferably palladium.

3) The process according to claim 1, where the catalytic hydrogenation of compound of formula II is carried out in an organic solvent.

4) The process according to claim 3, an organic solvent is alcohol like methanol, ethanol and more preferably in methanol.