Method for producing 5-chloro-
View Patent ↗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.
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)
comprising preparing 5-chlorothiophene-2-carbonyl chloride (IV) in a first step by chlorinating 5-chlorothiophene-2-carboxylic acid;
reacting said 5-chlorothiophene-2-carbonyl chloride (IV) in a second step with (2S)-3-aminopropane-1,2-diol hydrochloride (VII) to give N-((S)-2,3-dihydroxypropyl)-5-chlorothiophene-2-carboxamide (VIII);
converting said N-((S)-2,3-dihydroxypropyl)-5-chlorothiophene-2-carboxamide (VIII) in a third step to N-((S)-3-bromo-2-hydroxypropyl)-5-chlorothiophene-2-carboxamide (IX);
converting said N-((S)-3-bromo-2-hydroxypropyl)-5-chlorothiophene-2-carboxamide (IX) in a fourth step by reacting with 4-(4-aminophenyl)-3-morpholinone (III) to N-{(R)-2-hydroxy-3-[4-(3-oxomorpholin-4-yl)phenylamino]propyl}-5-chlorothiophene-2-carboxamide (X); and
reacting said N-{(R)-2-hydroxy-3-[4-(3-oxomorpholin-4-yl)phenylamino]propyl}-5-chlorothiophene-2-carboxamide (X) in a fifth step with phosgene or a phosgene equivalent.
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)