Pseudopolymorphic forms of a HIV protease inhibitor
New pseudopolymorphic forms of (3R,3aS,6aR)-hexahydrofuro [2,3-b] furan-3-yl (1S,2R)-3-[[(4-aminophenyl) sulfonyl] (isobutyl) amino]-1-benzyl-2-hydroxypropylcarbamate and processes for producing them are disclosed.
1. A process for preparing a pseudopolymorph of the compound (3R,3aS,6aR)-hexahydrofuro [2,3-b] furan-3-yl (1 S,2R)-3-[[(4-aminophenyl) sulfonyl] (isobutyl) amino]-1-benzyl-2-hydroxypropylcarbamate comprising
combining (3R,3aS,6aR)-hexahydrofuro [2,3-b] furan-3-yl (1 S,2R)-3-[[(4-aminophenyl) sulfonyl] (isobutyl) amino]-1-benzyl-2-hydroxypropylcarbamate with an organic solvent, water, or a mixture of water and a water miscible organic solvent, and inducing crystallization.
2. The process of claim 1 , wherein the pseudopolymorph is a hydrate solvate, alcohol solvate, alkane solvate, ketone solvate, ether solvate, cycloether solvate, ester solvate, or sulfonic solvate.
3. The process of claim 1 , wherein the pseudopolymorph is a hydrate solvate, C1-C4 alcohol solvate, C1-C4 chloroalkane solvate, C1-C5 ketone solvate, C1-C4 ether solvate, cycloether solvate, C1-C5 ester solvate, or C1-C4 sulfonic solvate.
4. The process of claim 1 , wherein the pseudopolymorph is Form A (ethanolate), Form B (hydrate), Form C (methanolate), Form D (acetonate), Form E (dichloromethanate), Form F (ethylacetate solvate), Form G (1-ethoxy-2-propanolate), Form H (anisolate), Form I (tetrahydrofuranate), Form J (isopropanolate), or Form K (mesylate).
5. The process of claim 1 , wherein the pseudopolymorph is a hydrate solvate.
6. The process of claim 1 , wherein the pseudopolymorph is a C1-C4 alcohol solvate.
7. The process of claim 1 , wherein the pseudopolymorph is an ethanolate solvate.
8. The process of claim 1 , wherein the pseudopolymorph is Form B (hydrate).
9. The process of claim 1 , wherein the pseudopolymorph is Form A (ethanolate).
10. The process of claim 1 , wherein the pseudopolymorph is prepared starting from the isopropanolate solvate of (3R,3aS,6aR)-hexahydrofuro [2,3-b] furan-3-yl (1 S,2R)-3-[[(4-aminophenyl) sulfonyl] (isobutyl) amino]-1-benzyl-2-hydroxypropylcarbamate.
11. The process of claim 1 , comprising combining (3R,3aS,6aR)-hexahydrofuro [2,3-b] furan-3-yl (1 S,2R)-3-[[(4-aminophenyl) sulfonyl] (isobutyl) amino]-1-benzyl-2-hydroxypropylcarbamate with a C1-C4 alcohol, water, or a mixture of a C1-C4 alcohol and water.
12. The process of claim 5 , wherein the ratio of compound to water in the pseudopolymorph ranges between 5:1 and 1:5.
13. The process of claim 5 , wherein the ratio of compound to water in the pseudopolymorph ranges between about 0.2:1 and about 3:1.
14. The process of claim 5 , wherein the ratio of compound to water in the pseudopolymorph ranges between about 1:1 and about 2:1.
15. The process of claim 5 , wherein the ratio of compound to water in the pseudopolymorph is about 1:1.
16. The process of claim 6 , wherein the ratio of compound to C1-C4 alcohol in the pseudopolymorph ranges between 5:1 and 1:5.
17. The process of claim 6 , wherein the ratio of compound to C1-C4 alcohol in the pseudopolymorph ranges between about 0.2:1 and about 3:1.
18. The process of claim 6 , wherein the ratio of compound to C1-C4 alcohol in the pseudopolymorph ranges between about 1:1 and about 2:1.
19. The process of claim 6 , wherein the ratio of compound to C1-C4 alcohol in the pseudopolymorph is about 1:1.