Process for the preparation of an orexin receptor antagonist

• US 9,012,636 B2
• Filed: 10/24/2011
• Issued: 04/21/2015
• Est. Priority Date: 10/29/2010
• Status: Active Grant

• Current Assignee: Merck Sharp & Dohme LLC (Merck & Co., Inc.)
• Original Assignee: Merck Sharp & Dohme Corporation (Merck & Co., Inc.)
• Inventors: Feng, Yun Shao, Moses, Anthony, Zhong, Yong-Li
• Primary Examiner(s): Jarrell, Noble
• Assistant Examiner(s): Kenyon, John S
• Application Number:
  US13/880,432
• Publication Number:
  US 20130324728A1
• Time in Patent Office: 1,275 Days
• US Class Current: 544/333
• CPC Class Codes: C07D 401/14 containing three or more hetero rings

Abstract

The present invention is directed to processes for preparing a pyridyl piperidine compound which is an antagonist of orexin receptors, and which is useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved.

Claims

1. A process for preparing a compound of the formula I:

2. The process of claim 1 wherein the organic base is a weak organic base.

3. The process of claim 1 wherein the organic base is selected from 2,6-lutidine, 2,4,6-lutidine, and Hunig'"'"'s base.

4. The process of claim 1 wherein 1-propylphosphonic anhydride is present at less than 10 mol %.

5. The process of claim 1 wherein the process is conducted in an amide solvent or acetonitrile.

6. The process of claim 5 wherein the process is conducted in an amide solvent which is selected from the group consisting of:

formamide, N-methylformamide, N,N-dimethylformamide, acetamide, N-methylacetate, N,N-dimethylacetamide, N,N,N′

,N′

-tetramethylurea, 2-pyrrolidone, and N-methylpyrrolidone.

7. The process of claim 6 wherein the amide solvent is N,N-dimethylformamide.

8. The process of claim 5 wherein the process is conducted in acetonitrile.

9. A process for increasing the purity of a compound of the formula I:

10. The process of claim 9 wherein the aromatic solvent is tert-butylbenzene.

11. The process of claim 9 wherein the aromatic solvent is toluene.

12. The process of claim 11 wherein the aromatic solvent additionally comprises heptane.