LFA-1 inhibitor and methods of preparation and polymorph thereof
Methods of preparation and purification of a compound of Formula I, intermediates thereof, a polymorph thereof, and related compounds are disclosed. Formulations and uses thereof in the treatment of LFA-1 mediated diseases are also disclosed.
1. A reaction mixture comprising
a compound of Formula I:
or a salt thereof;
a compound of Formula AA:
wherein R is a carbon-containing moiety or a silyl-containing moiety; and
a phase transfer catalyst.
2. The reaction mixture of claim 1 , further comprising one or more solvents.
3. The reaction mixture of claim 2 , wherein said one or more solvents are selected from the group consisting of water, acetone, methyl ethyl ketone, dioxane, and mixtures thereof.
4. The reaction mixture of claim 1 , further comprising water and acetone.
5. The reaction mixture of claim 1 , wherein said reaction mixture is biphasic.
6. The reaction mixture of claim 1 , further comprising a base.
7. The reaction mixture of claim 6 , wherein said base is sodium hydroxide.
8. The reaction mixture of claim 1 , wherein said phase transfer catalyst is a quaternary ammonium salt.
9. The reaction mixture of claim 8 , wherein said phase transfer catalyst is tetrabutylammonium hydroxide.
10. The reaction mixture of claim 1 , wherein R is a substituted or unsubstituted group selected from lower alkyl, lower alkenyl, lower alkynyl, cyclo(lower)alkyl, cyclo(lower)alkenyl, aryl, aralkyl, heterocyclyl, and heteroaryl groups.
11. The reaction mixture of claim 1 , wherein Formula AA is:
12. The reaction mixture of claim 11 , further comprising water, acetone, sodium hydroxide, and tetrabutylammonium hydroxide.
13. The reaction mixture of claim 1 comprising water, acetone and tetrabutylammonium hydroxide.
14. The reaction mixture of claim 13 , further comprising a pH modifier, wherein said reaction mixture has a pH of between about 1 and about 5.
15. The reaction mixture of claim 13 , wherein said reaction mixture heated above room temperature.