Process and solvate of 2-methyl-thieno-benzodiazepine

• US 5,703,232 A
• Filed: 01/16/1996
• Issued: 12/30/1997
• Est. Priority Date: 03/24/1995
• Status: Expired due to Term

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Tupper, David Edward, Hotten, Terrence Michael, Bunnell, Charles A., Larsen, Samuel D.
• Primary Examiner(s): Shah, Mukund J.
• Assistant Examiner(s): COLEMAN, BRENDA LIBBY
• Application Number:
  US08/586,431
• Time in Patent Office: 714 Days
• Field of Search: 514/220, 540/557
• US Class Current: 540/557
• 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 solvates of olanzapine. The invention provides a method for using such solvates of olanzapine to prepare substantially pure anhydrous Form I 2-methyl-thieno-benzodiazepine.

Claims

1. A process for preparing substantially pure Form I olanzapine comprising drying a C₁ -C₃ alcohol solvate of olanzapine, and then crystallizing the dried solvate with one or more solvents selected from ethyl acetate, acetone, 2-propanol, t-butanol, tetrahydrofuran and toluene.

2. A process of claim 1 wherein the solvate is contacted with the solvent at a temperature from about 25°

C. to 80°

C.

3. A process of claim 2 wherein the solvent is ethyl acetate.

4. A process of claim 3 wherein the solvate is a mono(methanol) solvate.

5. A process of claim 3 wherein the solvate is a mono(ethanol) solvate or a mono(2-propanol) solvate.

6. A process of claim 2 wherein the solvent is tetrahydrofuran.

7. A process of claim 6 wherein the solvent is mono(methanol) solvate.

8. A process of claim 6 wherein the solvate is a mono(ethanol) solvate or a mono(2-propanol) solvate.