Process for preparing amorphous cabazitaxel

Patent metadata

Field	Value
Publication number	US-9403785-B2
Application number	US-201214349332-A
Country	US
Kind code	B2
Filing date	Dec 26, 2012
Priority date	Jan 3, 2012
Publication date	Aug 2, 2016
Grant date	Aug 2, 2016

Abstract

The present invention provides a non-solvated amorphous form of (2α,5β,7β,10β,13α)-4-acetoxy-13-({(2R,3S)-3[ (tert-butoxy carbonyl) amino]-2-hydroxy-3-phenylpropanoyl}oxy)-1-hydroxy-7,10-dimethoxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate or Cabazitaxel (I),

and process for preparation thereof.

The present application also provides a non-solvated amorphous form of (2α,5β,7β,10β,13α)-4-acetoxy-13-({(2R,3S)-3[ (tert-butoxy carbonyl) amino]-2-hydroxy-3-phenylpropanoyl}oxy)-1-hydroxy-7,10-dimethoxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate or Cabazitaxel (I) having an XRPD pattern as per FIG. 1 , and IR spectrum as per FIG. 3 and is useful as an active pharmaceutical in a pharmaceutical composition comprising thereof and has anti-cancer activity.

First claim

We claim:

1. A non-solvated amorphous form of Cabazitaxel (I),

having up to 2% w/w or less of volatiles measured up to 160° C.

2. A non-solvated amorphous form of Cabazitaxel (I) having up to 2% w/w or less of volatiles measured up to 160° C. according to claim 1 , wherein an XRPD is having FIG. 1 and FT-IR is having FIG. 3 .

3. A process for the preparation of non-solvated amorphous form of Cabazitaxel having up to 2% w/w or less of volatiles measured up to 160° C., comprising the steps of:
i) coupling of 7,10-Dimethyl-10-DAB-III (a) with 3-(tert-butoxycarbonyl)-2-(4-methoxyphenyl)-4-phenyloxazolidine-5-carboxylic acid (b) to yield coupled product (c) in the presence of carbodiimide coupling agent;

ii) ring opening of coupled product (c) in the presence of an organic acid to give crude Cabazitaxel (I);

iii) optionally purifying the Cabazitaxel of step ii);
iv) combining Cabazitaxel or reaction material of step ii) or iii) with a polar organic solvent;
v) recovering the solvent; and
vi) isolating the material as non-solvated amorphous Cabazitaxel.

4. A process for preparation of non-solvated amorphous Cabazitaxel having up to 2% w/w or less of volatiles measured up to 160° C. according to claim 3 , wherein organic acid used in step ii) is selected from p-toluene sulfonic acid, C2 to C5 carboxylic acid, mono or di or tri halo substituted aliphatic carboxylic acid.

5. A process for preparation of non-solvated amorphous Cabazitaxel having up to 2% w/w or less of volatiles measured up to 160° C. according to claim 3 , wherein polar organic solvent used in step iv) is selected from C 1 -C 3 alcohol, 2-alkoxy ethanol or dimethylsulfoxide.

6. A process for preparation of non-solvated amorphous Cabazitaxel having up to 2% w/w or less of volatiles measured up to 160° C. according to claim 5 , wherein alkoxy group in 2-alkoxy ethanol solvent is comprised of alkyl group selected from C1 to C3 alkyl.

7. A process for preparation of non-solvated amorphous Cabazitaxel having up to 2% w/w or less of volatiles measured up to 160° C. according to claim 3 , wherein step v) of recovering the solvent is carried out under reduced pressure and at temperature ranging between 40° C.-60° C.

8. A process for the preparation of non-solvated amorphous Cabazitaxel having up to 2% w/w or less of volatiles measured up to 160° C., characterized by XRPD pattern as per FIG. 1 , from any known form of Cabazitaxel material, comprising the steps of:
i) combining Cabazitaxel or its solvate or anhydrous crystalline form with a polar organic solvent selected from methanol, 2-alkoxy ethanol, or dimethylsulfoxide;
ii) achieving dissolving of the reaction mass;
iii) recovering the solvent under reduced pressure and at temperature ranging between 40° C.-60° C.; and
iv) isolating the material as non-solvated amorphous Cabazitaxel.

9. A process for the preparation of non-solvated amorphous Cabazitaxel having up to 2% w/w or less of volatiles measured up to 160° C. according to claim 8 , wherein combining Cabazitaxel with a polar organic solvent in the step i) comprises dissolving at temperature ranging between 20 to 30° C.

Assignees

• Shilpa Medicare Ltd

Inventors

• Shrawat Vimal Kumar
• Purohit Prashant
• Dr Rafiuddin
• Singh Vinod Kumar
• Chaturvedi Akshay Kant

Classifications

• C07D305/14 Primary

  condensed with carbocyclic rings or ring systems · CPC title

• C07D413/12

  linked by a chain containing hetero atoms as chain links · CPC title