Claims for Patent: 8,883,805

Summary for Patent: 8,883,805

Title:	Process for the preparation of chiral 8-(3-aminopiperidin-1-yl)-xanthines
Abstract:	The invention relates to an improved process for preparing enantiomerically pure 8-(3-aminopiperidin-1-yl)-xanthines.
Inventor(s):	Waldemar Pfrengle, Thorsten Pachur, Thomas Nicola, Adil Duran
Assignee:	Boehringer Ingelheim International GmbH
Application Number:	US13/782,149
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,883,805
Patent Claims:	1. A compound of formula (II) or an enantiomer thereof, wherein R1 is a phenylcarbonylmethyl, benzyl, naphthylmethyl, pyridinylmethyl, pyrimidinyl-methyl, quinolinylmethyl, isoquinolinylmethyl, quinazolinylmethyl, quinoxalinylmethyl, naphthyridinylmethyl or phenanthridinylmethyl group wherein the aromatic or heteroaromatic moiety is in each case mono- or disubstituted by Ra, where the substituents may be the same or different and Ra is a hydrogen, fluorine, chlorine or bromine atom or a cyano, methyl, trifluoromethyl, ethyl, phenyl, methoxy, difluoromethoxy, trifluoromethoxy or ethoxy group, or two Ra radicals, when they are bonded to adjacent carbon atoms, may also be an —O—CH2—O— or —O—CH2—CH2—O— group, R2 is a methyl, ethyl, propyl, isopropyl, cyclopropyl or phenyl group, and R3 is a 2-buten-1-yl, 3-methyl-2-buten-1-yl, 2-butyn-1-yl, 2-fluorobenzyl, 2-chlorobenzyl, 2-bromobenzyl, 2-iodobenzyl, 2-methylbenzyl, 2-(trifluoromethyl)benzyl or 2-cyanobenzyl group. 2. The compound of formula (II) according to claim 1, wherein R1 is a phenylcarbonylmethyl, benzyl, naphthylmethyl, pyridinylmethyl, pyrimidinyl-methyl, quinolinylmethyl, isoquinolinylmethyl, quinazolinylmethyl, quinoxalinylmethyl or naphthyridinylmethyl group wherein the aromatic or heteroaromatic moiety is in each case mono- or disubstituted by Ra, where the substituents may be the same or different, and Ra is a hydrogen, fluorine or chlorine atom or a cyano, methyl, ethyl, methoxy or ethoxy group, R2 is a methyl, ethyl, propyl, isopropyl, cyclopropyl or phenyl group, and R3 is a 2-buten-1-yl, 3-methyl-2-buten-1-yl, 2-butyn-1-yl, 2-fluorobenzyl, 2-chlorobenzyl, 2-bromobenzyl, 2-iodobenzyl, 2-methylbenzyl, 2-(trifluoromethyl)benzyl or 2-cyanobenzyl group. 3. The compound of formula (II) according to claim 2, wherein R1 is a cyanobenzyl, (cyanopyridinyl)methyl, quinolinylmethyl, (methylquinolinyl)methyl, isoquinolinylmethyl, (methylisoquinolinyl)methyl, quinazolinylmethyl, (methylquinazolinyl)methyl, quinoxazinylmethyl, (methylquinoxalinyl)methyl, (dimethylquinoxalinyl)methyl or naphthyridinylmethyl group, R2 is a methyl, cyclopropyl or phenyl group, and R3 is a 2-buten-1-yl, 3-methyl-2-buten-1-yl, 2-butyn-1-yl, 2-chlorobenzyl, 2-bromobenzyl or 2-cyanobenzyl group. 4. The compound of formula (II) according to claim 3, wherein R1 is a (4-methylquinazolin-2-yl)methyl, (3-methylisoquinolin-1-yl)methyl or (3-cyanopyridin-2-yl)methyl group, R2 is a methyl group, and R3 is a 2-butyn-1-yl group. 5. The compound according to claim 4 of formula wherein R1 is a (4-methylquinazolin-2-yl)methyl, (3-methylisoquinolin-1-yl)methyl or (3-cyanopyridin-2-yl)methyl group, R2 is a methyl group, and R3 is a 2-butyn-1-yl group. 6. A compound of formula wherein R1 is a (4-methylquinazolin-2-yl)methyl group, R2 is a methyl group, and R3 is a 2-butyn-1-yl group. 7. A method of preparing a compound of formula or a physiologically tolerated salt thereof, said method comprising deprotecting a compound of formula wherein R1 is a (4-methylquinazolin-2-yl)methyl, (3-methylisoquinolin-1-yl)methyl or (3-cyanopyridin-2-yl)methyl group, R2 is a methyl group and R3 is a 2-butyn-1-yl group. 8. The method of claim 6, wherein the phthalyl protecting group of the compound of formula is detached; wherein R1 is a (4-methylquinazolin-2-yl)methyl group, R2 is a methyl group, and R3 is a 2-butyn-1-yl group. 9. The method according to claim 8, wherein the phthalyl protecting group is detached in the presence of ethanolamine. 10. The method according to claim 8, wherein the phthalyl protecting group is detached in the presence of i) ethanolamine and ii) in the presence of toluene or a mixture of tetrahydrofuran and water. 11. The method according to claim 8, further comprising crystallizing the deprotected compound from ethanol or methanol. 12. The method according to claim 8, wherein the deprotected compound is crystallized from ethanol. 13. Medicament comprising a compound obtained by the method according to claim 8, and optionally one or more inert carriers and/or diluents. 14. Medicament comprising a compound obtained by the method according to claim 12, and optionally one or more inert carriers and/or diluents.