Patent EA-002051-B1 (EA)
Title: Methods of making hiv-protease inhibitors
Inventor: WHITTEN KATHLEEN R
IPC: C07C69/86
Filed: 1997-09-04
Abstract: 1. A method of making a compound of formula (7)   comprising: converting under sufficient conditions a compound of formula 4   to the compound of formula 7 by: (a) contacting the compound of formula 4 with an organic solvent; (b) contacting the compound of formula 4 with methanesulfonic acid under conditions sufficient to form a compound of formula 7; and (c) spray drying the compound of formula 7. 2. A method according to claim 1, wherein the organic solvent is ethanol. 3. A method according to claim 1 further comprising converting a compound of formula (3)   wherein R1 is alkyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; or a group of formula   wherein R2 is an alkyl group, a cycloalkyl group, a heterncycloalkyl group, or O-R6, wherein R6 is an alkyl group, an aralkyl group, or an aryl group; or further wherein R1 is a group of formula   wherein each R3 is independently an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group; or further wherein R1 is a group of formula   wherein R4 and each R5 independently are an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group; and X is OH; OR7, wherein R7 is alkyl or aryl; halogen; pseudohalogen; OSQ2R8, wherein R8 is alkyl or aryl; heteroaryl bonded through the heteroatom; or N- hydroxyheterocyclic bonded through the oxygen; and wherein an alkyl group comprises preferably from 1 to 8, more preferably from 1 to 6, and most preferably from 1 to 4 carbon atoms; a cycloalkyl group is saturated or partially saturated , mono- or polycarbocyclic ring and preferably comprises from 5 to 14 carbon atoms in the ring; a heterocycloalkyl group is a non-aromatic univalent monocyclic, bicyclic or tricyclic radical, which is saturated or unsaturated , comprises from 3 to 18 atoms in the ring and contains from 1 to 5 heteroatoms selected from nitrogen, oxygen and sulfur; an aryl group is an aromatic, univalent monocyclic, bicyclic or tricyclic radical and comprises 6, 10, 14 or 18 carbon atoms in the ring; a heteroaryl group is an aromatic, univalent, monocyclic, bicyclic or tricyclic radical, comprises from 5 to 18 atoms in the ring and contains from 1 to 5 heteroatoms selected from nitrogen, oxygen and sulfur; in a compound of formula (4).  with the proviso that when R, is -CH3, X cannot be -OCH3 or -OH, and when R, is CH3C(O)-,.X cannot be -OH; or a pharmaceutically acceptable salt or solvate thereof. 4. A method according to claim 3, wherein R1 is -C(O)CH3. 5. A method according to claim 3, wherein X is Cl. 6. A method according to claim 5, wherein R1 is -C(O)CH3. 7. A method according to claim 3, wherein comprising converting the compound of formula (3) to compound (4) and deprotecting a compound of formula (5)   adding to the deprotected the compound of formula (5) a compound of formula (3). 8. A method according to claim 7, wherein in formula (3) R1 is -C(O)CH3. 9. A method according to claim 7, wherein in formula (3) X is Cl. 10. A method according to claim 9, wherein in formula (3) R1 is -C(O)CH3. 11. A method according to claim 3, wherein comprising converting a compound of formula (3) to compound (4) and combining the compound of formula (4) with the compound of formula (6):   12. A method according to claim 11, wherein in formula (3) R1 is -C(O)CH3.