Intermediate compounds and process for the preparation of lurasidone and salts thereof
AssigneeMapi Pharma Ltd.
InventorsEhud Marom, Michael Mizhiritskii, Susanna Tchilibon, Shai Rubnov
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Abstract
The present invention relates to a process for the preparation of Lurasidone or a pharmaceutically acceptable salt thereof, a compound useful for the treatment of schizophrenia and bipolar disorder. The present invention further relates to processes for the preparation of Lurasidone intermediates, and to certain novel intermediates obtained by such processes.
Claims21
1-28. (canceled)
A process for the preparation of a compound of formula (1′), or a salt thereof, which comprises:
- (a) reacting a compound of formula A′ with a compound of formula B′ to form a compound of formula C′:
- and
- (b) reacting a compound of formula C′ with a compound of formula D to form a compound of formula 1′, or a salt thereof
- wherein
- X is selected from O and NH;
- Y and Y′ are independently selected from OH, OSO2R, NH2, and Hal, or Y and Y′ together are N (CH2CH2Z)2 wherein Z is selected from OH, OSO2R, and Hal;
- Y″ is selected from OH, OSO2R, NH2, Hal, and N(CH2CH2Z)2;
- Y′″ is selected from NH2 and piperazinyl;
- Hal is selected from Cl, Br, and I;
- and
- R is selected from substituted or unsubstituted alkyl and aryl.
A process for the preparation of 3-(1-piperazinyl)-1,2-benzisothiazole of the formula
- comprising the steps of:
- a) sulfonation of 1,2-benzisothiazol-3(2H)-one of the formula
- using a sulfonating reagent;
- b) reacting the sulfonated compound resulting from step (a) with a compound of the general formula
- so as to obtain a compound of the general formula:
- wherein Z′ is selected from OH, OSO2R, and Hal;
- R is selected from substituted
- or unsubstituted alkyl and aryl;
- and Hal is halogen;
- and
- c) reacting the obtained compound with ammonia or a derivative thereof so as to obtain 3-(1-piperazinyl)-1,2-benzisothiazole.
A compound of formula B′ having the following structure:
- wherein Y and Y′ together form a zwitterion N{circle around (+)}(CH2CH2Z)2 Z′{circle around (−)};
- Z is selected from OH, OSO2R, and Hal;
- Z′ is selected from OSO2R, and Hal;
- Hal is selected from Cl, Br, and I;
- and R is selected from substituted or unsubstituted alkyl and aryl,
- wherein the compound is a racemate;
- or
- wherein the compound is in an enantiomerically enriched or pure form.
A compound of formula C having the following structure:
- wherein Y″ is selected from NH2, N(CH2CH2OH)2, N(CH2CH2Hal)2, N(CH2CH2OSO2R)2, OH, OSO2R, and Hal;
- Hal is selected from Cl, Br, and I;
- and R is selected from substituted or unsubstituted alkyl and aryl,
- wherein the compound is a racemate;
- or
- wherein the compound is in an enantiomerically enriched or pure form.
A compound having the following structure:
- wherein Z″ is selected from OH, OSO2R, and Hal;
- Hal is selected from Cl, Br, and I;
- and R is selected from substituted or unsubstituted alkyl and aryl.
Dependencies are inferred from the claim text.