Process for obtaining 4-(N-alkylamino)-5,6-dihydro-4H-thien-(2,3-b)-thiopyran-2-sulfonamide-7,7-dioxides and intermediates
AssigneeRagatives, S.L.
InventorsPablo García Losada, Luis Octavio Silva Guisasola, Antonio Lorente Bonde-Larsen, Jorge Martín Juárez
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Abstract
The process for obtaining 4-(N-alkylamino)-5,6-dihydro-4H-thien-(2,3-b)-thiopyran-2-sulfonamide-7,7-dioxides (I) wherein R1 is H or C1-5 alkyl, and R2 is C1-5 alkyl, starts from the corresponding 4-(N-alkylamino)-5,6-dihydro-4H-thien-(2,3-b)-thiopyran-7,7-dioxides, and comprises protecting the alkylamine group, introducing a sulfonamide group and eliminating protecting group. Some compounds of formula (I) are inhibitors of the carbonic anhydrase and can be used in the treatment of elevated intraocular pressure
Claims29
A process for obtaining 4-(N-alkylamino)-5,6-dihydro-4H-thien-(2,3-b)-thiopyran-2-sulfonamide-7,7-dioxides of general formula (I)
- wherein
- R1 is H or C1-5 alkyl, and
- R2 is C1-5 alkyl,
- their individual cis or trans diastereomers, their individual levo or dextro enantiomers, or isomeric mixtures thereof, and pharmaceutically acceptable salts thereof, which comprises
- a) protecting the nitrogen present in the aminosulfone of formula (II)
- wherein R1 and R2 have been defined earlier, with a nitrogen protecting group to obtain an N-protected aminosulfone of formula (III)
- wherein R1 and R2 are as previously defined and P is a nitrogen protecting group;
- b) introducing a sulfonamide group at position 2 of said N-protected aminosulfone (III) to obtain the sulfonamide intermediate of formula (VI)
- wherein R1 and R2 are as previously defined and P is a nitrogen protecting group;
- and
- c) eliminating the nitrogen protecting group to obtain the compound of formula (I).
An intermediate of general formula (III)
- wherein
- R1 is H or C1-5 alkyl,
- R2 is C1-5 alkyl, and
- P is a nitrogen protecting group;
- its individual cis or trans diastereomers, its individual levo or dextro enantiomers, or isomeric mixtures thereof.
An intermediate of general formula (IV)
- wherein
- R1 is H or C1-5 alkyl,
- R2 is C1-5 alkyl, and
- P is a nitrogen protecting group;
- its individual cis or trans diastereomers, its individual levo or dextro enantiomers, or isomeric mixtures thereof.
An intermediate of general formula (V)
- wherein
- R1 is H or C1-5 alkyl,
- R2 is C1-5 alkyl, and
- P is a nitrogen protecting group;
- its individual cis or trans diastereomers, its individual levo or dextro enantiomers, or isomeric mixtures thereof.
An intermediate of general formula (VI)
- wherein
- R1 is H or C1-5 alkyl,
- R2 is C1-5 alkyl, and
- P is a nitrogen protecting group;
- its individual cis or trans diastereomers, its individual levo or dextro enantiomers, or isomeric mixtures thereof.
A chiral aminosulfone selected from the group consisting of:
- i) (4S-trans)-4-(N-alkylamino)-5,6-dihydro-6-alkyl-4H-thien-(2,3-b)-thiopyran-7,7-dioxide (IIa)
- wherein
- R1a and R2a, independently, are C1-5 alkyl, and
- ii) (4S)-(N-alkylamino)-5,6-dihydro-4H-thien-(2,3-b)-thiopyran-7,7-dioxide (IIb)
- wherein
- R1b is H, and
- R2b is C1-5 alkyl.
Dependencies are inferred from the claim text.