Method for producing 5-chloro- N -({(5 S )-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide

• US 8,106,192 B2
• Filed: 09/09/2009
• Issued: 01/31/2012
• Est. Priority Date: 01/07/2003
• Status: Active Grant

• Current Assignee: Bayer Intellectual Property GmbH (Bayer AG)
• Original Assignee: Bayer Pharma AG (Bayer AG)
• Inventors: Thomas, Christian R.
• Primary Examiner(s): Anderson, Rebecca
• Assistant Examiner(s): SHTERENGARTS, SAMANTHA L
• Application Number:
  US12/556,158
• Publication Number:
  US 20100081807A1
• Time in Patent Office: 874 Days
• Field of Search: 544/137, 544/146, 549/72
• US Class Current: 544/137
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 333/38 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/14 containing three or more hetero rings

Abstract

The invention relates to a method for producing 5-chloro-N-({5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)-phenyl]-1,3-oxazolidin-5-yl}-methyl)-2-thiophenecarboxamide starting from 5-chlorothiophene-2-carbonyl chloride, (2S)-3-amino-propane-1,2-diol and 4-(4-aminophenyl)-3-morpholinone.

Claims

1. A process for preparing 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide of the formula (I)

2. A process for preparing N-{(R)-2-hydroxy-3-[4-(3-oxomorpholin-4-yl)phenylamino]propyl}-5-chlorothiophene-2-carboxamide (X), comprising reacting N-((S)-3-bromo-2-hydroxypropyl)-5-chlorothiophene-2-carboxamide (IX) with 4-(4-aminophenyl)-3-morpholinone (III).

3. A process for preparing 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide of the formula (I), comprising reacting N-{(R)-2-hydroxy-3-[4-(3-oxomorpholin-4-yl)phenylamino]propyl}-5-chlorothiophene-2-carboxamide (X) with phosgene or a phosgene equivalent and further comprising preparing said N-{(R)-2-hydroxy-3-[4-(3-oxomorpholin-4-yl)phenylamino]propyl}-5-chlorothiophene-2-carboxamide (X) by reacting N-((S)-3-bromo-2-hydroxypropyl)-5-chlorothiophene-2-carboxamide (IX) with 4-(4-aminophenyl)-3-moxpholinone (III).

4. The process as claimed in claim 3, characterized in that the phosgene equivalent is N,N-carbonyldiimidazole.

5. The process as claimed in claim 4, characterized in that from 1.1 to 1.3 equivalents of N,N-carbonyldiimidazole are used.

6. The process of claim 3, wherein the reaction takes place in a solvent mixture of 1-methyl-2-pyrrolidone and toluene.

7. The process of claim 3, further comprising preparing the N-((S)-3-bromo-2-hydroxypropyl)-5-chlorothiophene-2-carboxamide (IX) by reacting N-((S)-2,3-dihydroxypropyl)-5-chlorothiophene-2-carboxamide (VIII) with hydrobromic acid in acetic acid.

8. The process of claim 7, further comprising preparing said N-((S)-2,3-dihydroxypropyl)-5-chlorothiophene-2-carboxamide (VIII) by reacting 5-chlorothiophene-2-carbonyl chloride (IV) with (2S)-3-aminopropane-1,2-diol hydrochloride (VII).

9. N-((S)-3-Bromo-2-hydroxypropyl)-5-chlorothiophene-2-carboxamide of the formula (IX)