Details for Patent: 7,279,582

Title:	Retroviral protease inhibiting compounds
Abstract:	A compound of the formula: ##STR00001## is disclosed as an HIV protease inhibitor. Methods and compositions for inhibiting an HIV infection are also disclosed.
Inventor(s):	Stoner; Eric J. (Kenosha, WI), Cooper; Arthur J. (Lake Villa, IL), Kolaczkowski; Lawrence (Gurnee, IL), Patel; Ketan M. (Arlington Heights, IL), Sham; Hing Leung (Mundelein, IL), Norbeck; Daniel W. (Crystal Lake, IL), Chen; Xiaoqi (Libertyville, IL), Betebenner; David A. (Gurnee, IL), Herrin; Thomas R. (Waukegan, IL), Kumar; Gondi N. (Round Lake Beach, IL), Condon; Stephen L. (Kenosha, WI), Dickman; Daniel A. (Grayslake, IL), Oliver; Patricia A. (Lindenhurst, IL), Tien; Jien-Heh J. (Libertyville, IL)
Assignee:	Abbott Laboratories (Abbott Park, IL)
Filing Date:	Oct 25, 2002
Application Number:	10/280,652
Claims:	1. A process for the preparation of (2S, 3S, 5S)-2-(2,6-dimethylphenoxyacetyl)amino-3-hydroxy-5-(2S-(1-tetrahydro-pyri- mid-2-onyl)-3-methyl butanoyl)amino-1,6-diphenylhexane, or a pharmaceutically acceptable salt, ester or prodrug thereof, comprising reacting (2S, 3S, 5S)-2-amino-3-hydroxy-5-(2S-(1-tetrahydro-pyrimid-2-onyl)-3-methyl butanoyl)amino-1,6-diphenylhexane with 2,6-dimethylphenoxyacetic acid, or a salt or an activated ester derivative thereof. 2. The process according to claim 1 wherein (2S,3S,5S)-2-amino-3-hydroxy-5-(2S-(1-tetrahydro-pyrimid-2-onyl)-3-methyl butanoyl)amino-1,6-diphenylhexane is reacted with 2,6-dimethylphenoxyacetyl chloride. 3. A process for the preparation of (2S,3S,5S)-2-(2,6-dimethylphenoxyacetyl)amino-3-hydroxy-5-(2S-(1-tetrahyd- ro-pyrimid-2-onyl)-30methyl butanoyl)amino-1,6-diphenylhexane, or a pharmaceutically acceptable salt, ester or prodrug thereof, comprising (a) reacting (2S,3S,5S)-2-N,N-dibenzylamino-3-hydroxy-5-amino-1,6-diphenylhexane with 2S-(1-tetrahydro-pyrimid-2-onyl)-3-methyl butanoic acid or a salt or activated ester derivative thereof to provide (2S,3S,5S)-2-N,N-dibenzylamino-3-hydroxy-5-(2S-(1-tetrahydro-pyrimid-2-on- yl)-3-methyl butanoyl)amino-1,6-diphenylhexane; (b) debenzylating the product of step (a) to provide (2S,3S,5S)-2-amino-3-hydroxy-5-(2S-(1-tetrahydro-pyrimid-2-onyl)-3-methyl butanoyl)amino-1,6-diphenylhexane; and (c) reacting the product of step (b) with 2,6-dimethylphenoxyacetic acid, or a salt or an activated ester derivative thereof. 4. The process according to claim 3 wherein (a) (2S,3S,5S)-2-N,N-dibenzylamino-3-hydroxy-5-amino-1,6-diphenylhexane is reacted with 2S-(1-tetrahydro-pyrimid-2-onyl)-3-methyl butanoyl chloride to provide (2S,3S,5S)-2-N,N-dibenzylamino-3-hydroxy-5-(2S-(1-tetrahydro-pyrimid-2-on- yl)-3-methyl butanoyl)amino-1,6-diphenylhexane; (b) the product of step (a) is hydrogenated to provide (2S,3S,5S)-2-amino-3-hydroxy-5-(2S-(1-tetrahydro-pyrimid-2-onyl)-3-methyl butanoyl)amino-1,6-diphenylhexane; and (c) the product of step (b) is reacted with 2,6-dimethylphenoxyacetyl chloride. 5. A process for the preparation of (2S,3S,5S)-2-(2,6-Dimethylphenoxyacetyl)amino-3-hydroxy-5-(2S-(1-tetrahyd- ro-pyrimid-2-onyl)-3-methyl butanoyl)amino-1,6-diphenylhexane, or a pharmaceutically acceptable salt, ester or prodrug thereof, as an amorphous solid, comprising dissolving (2S,3S,5S)-2-(2,6-Dimethylphenoxyacetyl)amino-3-hydroxy-5-(2S-(1-tetrahyd- ro-pyrimid-2-onyl)-3-methyl butanoyl)amino-1,6-diphenylhexane in an organic solvent, followed by adding the solution to water. 6. The process according to claim 5 wherein (2S,3S,5S)-2-(2,6-Dimethylphenoxyacetyl)amino-3-hydroxy-5-(2S-(1-tetrahyd- ro-pyrimid-2-onyl)-3-methyl butanoyl)amino-1,6-diphenylhexane is dissolved in ethanol (from about 2 to about 4 mL/g) and the ethanolic solution is added to water (from about 10 about 100 mL/g).