Process for the preparation of fingolimod and its salts

Patent metadata

Field	Value
Publication number	US-9732030-B2
Application number	US-201414759224-A
Country	US
Kind code	B2
Filing date	Jan 11, 2014
Priority date	Jan 17, 2013
Publication date	Aug 15, 2017
Grant date	Aug 15, 2017

Abstract

The present invention provides process for preparation of Fingolimod hydrochloride (I).

Fingolimod hydrochloride (I) as Form-β obtained by the process of present invention may be useful as active pharmaceutical ingredient in pharmaceutical compositions for the treatment of autoimmune related disorder including multiple sclerosis.

First claim

The invention claimed is:

1. A process for preparing Fingolimod hydrochloride (I), comprising the steps of—
a) providing a solution of Fingolimod base with an ester or a halohydrocarbon organic solvent used in the range up to more than 20 times (by volume) but less than 50 times (by volume) with respect to weight of Fingolimod free base;
b) raising the temperature to a range between 35 to 75° C.;
c) optionally adding activated carbon followed by filtering;
d) adding 5-10% isopropanol-hydrochloric acid solution; and
e) isolating the Fingolimod hydrochloride crystalline Form-β;
the said crystalline Form-β being characterized by x-ray powder diffraction pattern having, characteristic 2θ° peaks in XRPD peak set of 3.54, 7.10, 10.67, 15.36, 17.83, 20.53, 21.49, 23.29, 25.12, 26.68 and 29.22±0.1 2θ°; un-split peak near at 20.5 2θ° and DSC isotherm comprising endothermic peaks selected from peak-1: ranging between 40 to 45° C., peak-2: ranging between 65 to 70° C. and peak-3: ranging between 107 to 115° C.

2. A process for preparing Fingolimod hydrochloride (I) according to claim 1 , wherein the Fingolimod hydrochloride obtained as crystalline Form-β is characterized by X-ray powder diffraction pattern comprising characteristic 2θ° peaks in XRPD peak set of 3.54, 7.10, 10.67, 15.36, 20.53, 21.49 and 25.12±0.1 2θ° and DSC isotherm comprising endothermic peaks selected from Peak-1: ranging between 40 to 45° C., Peak-2: ranging between 65 to 70° C. and Peak-3: ranging between 107 to 115° C.

3. A process for preparing Fingolimod hydrochloride (I) according to claim 1 , wherein the Fingolimod hydrochloride obtained as crystalline Form-β is further characterized by:
i. X-ray powder diffraction pattern comprising an un-split peak near at 20.5 2θ°;
ii. Other characteristic 2θ° peaks selected from the XRPD peak set of 17.83 , 23.29, 26.68 and 29.22±0.1 2θ.

4. A process for preparing Fingolimod hydrochloride (I) according to claim 1 , wherein the Fingolimod hydrochloride obtained as crystalline Form-β is further characterized by, particle size distribution of d(0.1): 10-20 μm; d(0.5): 25-35 μm and d(0.9): 45-65 μm.

Assignees

• Shilpa Medicare Ltd

Inventors

• Shrawat Vimal Kumar
• Dr Rafiuddin
• Chaturvedi Akshaykant

Classifications

• C07C213/00 Primary

  Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton · CPC title

• C07C231/12

  by reactions not involving the formation of carboxamide groups · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07C233/31

  with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom · CPC title

• C07C233/18

  having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton · CPC title