Granted Patent
B2
US 12,195,464 · App. 17/652,076 · Granted Jan 14, 2025
Lumateperone bis-tosylate salts and crystals and methods for manufacture thereof
Assignee:
INTRA-CELLULAR THERAPIES, INC.
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Abstract
The disclosure provides a new, stable, pharmaceutically acceptable bis-tosylate salt form of 1-(4-fluoro-phenyl)-4-((6bR,10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H,7H-pyrido[3′,4′: 4,5]pyrrolo[1,2,3-de]quinoxalin-8-yl)-butan-1-one: together with methods of making and using them, and pharmaceutical compositions comprising them.
Claims (11)
1. A method of making a bis-tosylate salt of 1-(4-fluorophenyl)-4-((6bR,10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H,7H-pyrido[3′,4′: 4,5]pyrrolo[1,2,3-de]quinoxalin-8-yl)-butan-1-one, comprising the steps of:
(a) reacting 1-(4-fluoro-phenyl)-4-((6bR,10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H,7H-pyrido[3′,4′: 4,5]pyrrolo[1,2,3-de]quinoxalin-8-yl)-butan-1-one (ITI-007) free base with toluenesulfonic acid at a molar ratio of about 1:1, in a solvent consisting of 2-butanone; and
(b) recovering the salt thus formed as a crystalline solid by crystallization from the 2-butanone solvent, wherein the salt recovered contains less than 3 wt % of any other ITI-007 tosylate salt form, by weight of the salt.
2. The method according to claim 1 , wherein in step (a) the salt is formed from a slurry of the ITI-007 free base and the toluenesulfonic acid in the 2-butanone solvent.
3. The method according to claim 1 , wherein in step (b) the salt recovered contains less than 2 wt % of any other ITI-007 tosylate salt form, by weight of the salt.
4. The method according to claim 1 , wherein the reaction of step (a) is carried out using the ITI-007 free base at a concentration of about 1 gram per 20 mL of the 2-butanone solvent.
5. The method according to claim 1 , wherein in step (b) the salt recovered is isolated by filtration from the 2-butanone solvent to yield the crystalline solid.
6. The method according to claim 1 , wherein the reaction of step (a) occurs at room temperature.
7. The method according to claim 1 , wherein in step (b) the salt recovered contains less than 1 wt % of any other ITI-007 tosylate salt form, by weight of the salt.
8. The method according to claim 1 , wherein in step (b) the salt recovered contains less than 5 wt % of ITI-007 free base form, by weight of the salt.
9. The method according to claim 1 , wherein in step (b) the salt recovered contains less than 1 wt. % of any amorphous forms of ITI-007, by weight of the salt.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Mar 23, 2022
From: LI, PENG
To: INTRA-CELLULAR THERAPIES, INC.
Reel/Frame 059374/0879 →
Continuity (4)
Continuation
PCTUS2019035845
· Jun 6, 2019
Provisional Application
62681534
· Jun 6, 2018
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