Process for preparing rivaroxaban using intermediates

摘要

The present inventors have surprisingly found that rivaroxaban of formula I can be prepared in a one-pot process, in high purity and with high yield, by reacting 5-chlorothiophene-2-carboxylic acid or a salt thereof with a sulfonylating agent to produce a sulfonyl ester intermediate, which is then condensed with 4-[4-[(SS)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl]morpholine-3-one or an acid addition salt thereof to produce rivaroxaban.

主权项

1. A one-pot process for preparing rivaroxaban, 5-chloro-N-[[(5S)-2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]oxazolidin-5-yl]methyl]thiophene-2-carboxamide, of formula I: or a stereochemically isomeric form or a racemic mixture thereof, comprising: a) reacting 5-chlorothiophene-2-carboxylic acid of formula IV: or a salt thereof, with a sulfonylating agent of formula Va or Vb: wherein ‘R’ is an alkyl, cycloalkyl, haloalkyl, aralkyl, or substituted or unsubstituted aryl group;to produce a sulfonyl ester compound of formula III: wherein R is as defined above; b) reacting the sulfonyl ester compound of formula III with 4-[4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl]morpholine-3-one of formula II: or a stereochemically isomeric form or a racemic mixture thereof, or an acid addition salt thereof, to produce the rivaroxaban of formula I or a stereochemically isomeric form or a racemic mixture thereof.