Preparation of fingolimod and its salts
AssigneeDr. Reddy's Laboratories, Inc.
InventorsSrinivas Katkam, Rajeswar Reddy Sagyam, Raghavendar Rao Morthala, Babu Ireni, Krishna Vinigari, Suresh Kumar Ramdoss, Srinivasulu Rangineni, Arjunkumar Tummala, Javed Iqbal, Srinivas Oruganti, Bhaskar Kandagatla
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Abstract
The present application provide processes for the preparation of fingolimod and its pharmaceutically acceptable salts, process for the purification of fingolimod hydrochloride and process for the preparation of amorphous fingolimod hydrochloride.
Claims35
A process for the preparation of fingolimod of formula (Ia)
- or its salt comprising:
- a) reducing 3-nitro-1-(4-octylphenyl)propan-1-one of formula (VI):
- using a Lewis acid and a trialkyl silane to obtain a compound of formula (VII);
- and
- b) reacting the compound of formula (VII):
- with paraformaldehyde to obtain a compound of formula (VIII);
- and
- c) reacting the compound of formula (VIII) with a reducing agent to obtain fingolimod of formula (Ia):
- or its salt.
A process for the preparation of fingolimod of formula (Ia)
- or its salt comprising;
- a) reducing octanophenone of formula (II):
- using a Lewis acid and a trialkyl silane to obtain octylbenzene of formula (III);
- b) reacting the compound of formula (III) with a 3-halopropionyl halide to obtain a compound of formula (IV):
- wherein X is a halogen;
- c) reacting the compound of formula (IV) with a compound of formula (V):
- M+n(NO2)n (V)
- wherein M is a metal ion and n is 1, 2, or 3 to obtain a compound of formula (VI);
- and
- d) converting the compound of formula (VI) to fingolimod of formula (Ia):
- or its salt.
A process for the preparation of fingolimod of formula (Ia)
- or its salt comprising:
- a) reacting the compound of formula (VII):
- with paraformaldehyde in the presence of a base to obtain a compound of formula (VIII);
- and
- b) reacting the compound of formula (VIII) with a reducing agent to obtain fingolimod of formula (Ia):
- or its salt.
A process for the purification of fingolimod hydrochloride, comprising:
- (a) providing a solution of fingolimod hydrochloride in methanol or methanol and ethyl acetate mixture;
- (b) optionally adding ethyl acetate;
- (c) cooling the solution to a temperature below 10° C.;
- (d) isolating fingolimod hydrochloride.
A process for the preparation of amorphous fingolimod hydrochloride, comprising:
- a) providing a solution of fingolimod hydrochloride and a pharmaceutically acceptable carrier in a solvent;
- and
- b) obtaining amorphous fingolimod hydrochloride.
Fingolimod hydrochloride having purity greater than 99.8% with less than about 0.1% of each of the compound given in the table below:
- Code
- Structure
- Impurity A
- Impurity B
- Impurity C
- Impurity D
- Impurity E
- Impurity F
- Impurity G
- Impurity H
- Impurity I
Dependencies are inferred from the claim text.