Process and solvate of 2-methyl-thieno-benzodiazepine

• US 5,631,250 A
• Filed: 03/24/1995
• Issued: 05/20/1997
• Est. Priority Date: 03/24/1995
• Status: Expired due to Term

• Current Assignee: Eli Lilly and Company, Lilly Industries Limited
• Original Assignee: Eli Lilly and Company, Lilly Industries Limited
• Inventors: Larsen, Samuel D., Tupper, David E., Bunnell, Charles A., Hotten, Terrence M.
• Primary Examiner(s): McKane, Joseph
• Assistant Examiner(s): MYERS, RICHARD
• Application Number:
  US08/410,474
• Time in Patent Office: 788 Days
• Field of Search: 540/557, 514/220
• US Class Current: 514/220
• CPC Class Codes: C07D 495/04 Ortho-condensed systems

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.

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°

C. to about 130°

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.