Chlorine → HCID 19003523, compound
Reaction equation
[C:1]([C:4]1[CH:8]=[C:7]([Cl:9])[S:6][C:5]=1[S:10](N)(=O)=O)(=[O:3])[CH3:2].[Cl:14]Cl>>[C:1]([C:4]1[CH:8]=[C:7]([Cl:9])[S:6][C:5]=1[S:10][Cl:14])(=[O:3])[CH3:2]Participants
Procedure
The process comprises displacing the C(2)-chloro of 3-acetyl-2,5-dichlorothiophene (1) with benzyl mercaptide to form the thioether of structure (2), which is then converted to 3-acetyl-5-chloro-2thiophenesulfonamide (3) by reaction with chlorine to form 3-acetyl-5-chloro-2-thiophenesulfenyl chloride, followed by reaction with ammonia to form 3-acetyl-5-chloro-2-thiophenesulfenamide, and finally oxidation. Bromination provides 3-bromoacetyl-5-chloro-2-thiophenesulfonamide (4), which is converted to (S)-3,4-dihydro-6-chloro-4-hydroxy-2H-thieno[3,2-e]-1,2-thiazine-1,1-dioxide (5) by reduction with (+)-β-chlorodiisopinocampheylborane followed by treatment with aqueous base. Alkylation at N(2) provides the (S)-3,4-dihydro-6-chloro-4-hydroxy-2-substituted-2H-thieno[3,2-e]-1,2-thiazine-1,1-dioxide of structure (6). Formation of the C(6) anion is accomplished by halogen-metal exchange, and the anion is reacted with sulfur dioxide to form a lithium sulfinate, which upon reaction with hydroxylamine-0-sulfonic acid provides the (S)-3,4-dihydro-4-hydroxy-2-substituted-2H-thieno[ 3,2-e]-1,2-thiazine-6-sulfonamide-1,1-dioxide of structure (7). Protection of the C(6)-sulfonamide functionality, followed by activation of the C(4)-hydroxyl and displacement with an appropriate amine provides the (R)-3,4-dihydro-4-alkylamino-2-substituted-2H-thieno[3,2-e]-1,2-thiazine-6-sulfonamide-1,1-dioxide of structure I.
Sources & evidence
- ORD record
- ord-39f133ac974240439a0908eebac91bf1
- Source dataset
- uspto-grants-1994_09
- Patent number
- US05344929
Reaction notes
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