Process for the preparation of an orexin receptor antagonist

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

or a pharmaceutically acceptable salt thereof,

which comprises:

contacting a compound of the formula II:

with trimethylacetyl chloride in the presence of an organic base,

followed by contacting the resultant product with a compound of the formula III:

in the presence of 1-propylphosphonic anhydride, wherein the 1-propylphosphonic anhydride is present at less than a stochiometric amount,

to give the 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:

or a pharmaceutically acceptable salt thereof,

which comprises:

crystallizing the compound of the formula I from a solvent which comprises an aromatic solvent selected from the group consisting of tert-butylbenzene, o-xylene, p-xylene, cumene, ethylbenzene and toluene.

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.