Process for the preparation of high pure eribulin and its mesylate salt
AssigneeNatco Pharma Limited
InventorsPrabhakar DIVYA, Srinivasu KASA, Durga Prasad KONAKANCHI, Ramesh DANDALA, Pulla Reddy MUDDASANI, Venkaiah Chowdary NANNAPANENI
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Abstract
The present invention relates to a process for the preparation of high pure Eribulin and Eribulin Mesylate. The present invention involves preparation of high pure Eribulin and its mesylate salt involving chiral acid addition salts of Eribulin.
Claims10
A process for the preparation of high pure Eribulin mesylate comprising the steps of:
- (i) reacting Eribulin free base of formula-I,
- with a chiral acid of formula-III,
- R—C(X)(Y)COOH (III)
- wherein
- R=aryl, alkyl, aralkyl, substituted aryl, heteroaryl, substituted heteroaryl, etc.
- X═H, alkyl, etc.
- Y═NHZ, where Z═SO2R′, COR′, where R′=aryl, alkyl, aralkyl, substituted aryl, heteroaryl, substituted heteroaryl,
- to form a chiral acid addition salt of formula-IV,
- R—C(X)(Y)COO−Eribulin (formula-IV)
- wherein R, X, and Y are as defined above;
- (ii) purifying the chiral acid addition salt of formula-IV in a suitable solvent to get pure chiral acid addition salt,
- (iii) neutralizing the acid addition salt of formula-IV with a base to get high pure Eribulin after extracting into a solvent and distilling of the solvent,
- (iv) converting the pure Eribulin base to mesylate salt.
A process for the preparation of high pure Eribulin comprising the steps of:
- a) reacting Eribulin free base with a protected chiral acid to form corresponding acid addition salt of Eribulin,
- b) purifying the acid addition salt of Eribulin by recrystallization to control the related impurities,
- c) treating the salt with a base to liberate high pure Eribulin,
- d) optionally converting the high pure Eribulin to Eribulin mesylate.
A process for the preparation of Eribulin mesylate by treating pure Eribulin base with ammonium methanesulfonate.
Eribulin base having the purity of more than 99%.
Eribulin mesylate is having the purity of more than 99%, preferably more than 99.5%.
Chiral acid addition salt of Eribulin is selected from,
Dependencies are inferred from the claim text.