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|Title:||Process and solvate of 2-methyl-thieno-benzodiazepine|
|Abstract:||The invention provides lower alcohol solvates of 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine (olanzapine) and a process for making such lower alcohol solyates of olanzapine. The invention provides a method for using such solyates of olanzapine to prepare substantially pure anhydrous Form I 2-methyl-thieno-benzodiazepine.|
|Inventor(s):||Bunnell; Charles A. (Lafayette, IN), Hotten; Terrence M. (Farnborough, GB2), Larsen; Samuel D. (West Lafayette, IN), Tupper; David E. (Reading, GB2)|
|Assignee:||Eli Lilly and Company (Indianapolis, IN) Lilly Industries Limited (Basingstoke, GB2)|
|Filing Date:||Mar 24, 1995|
|Claims:||1. A crystalline mono methanol solvate form of a compound of the Formula I ##STR3## |
2. A crystalline mono ethanol solvate form of a compound of the Formula I ##STR4##
3. A crystalline mono 1-propanol solvate form of a compound of the Formula I ##STR5##
4. A process for preparing a lower alcohol solvate comprising preparing technical olanzapine which comprises contacting intermediate 1 ##STR6## with dimethylsulfoxide and N-methylpiperazine with heating at about 90.degree. C. to about 130.degree. C.; and
crystallizing olanzapine from the reaction mixture with a solvent selected from the group consisting of lower alcohols to provide the corresponding lower alcohol solvate of olanzapine.
5. A method of claim 4 wherein the lower alcohol is methanol.
6. A method of claim 4 wherein the lower alcohol is ethanol.
7. A method of claim 4 wherein the lower alcohol is 1-propanol.
8. A method of claim 4 further comprising converting the resulting lower alcohol solvate into olanzapine.
9. A method of claim 8 wherein olanzapine is substantially pure Form I.
10. A method of claim 8 wherein the lower alcohol solvate is the methanolate.
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