Pyridine → n-(4-Methanesulfonylamino-2-sulfamoylphenyl)malonamic acid methyl ester
Reaction equation
[CH3:1][S:2]([NH2:5])(=[O:4])=[O:3].[CH3:6][S:7](Cl)(=[O:9])=[O:8].[N:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.Cl[C:18](=[O:24])[CH2:19][C:20]([O:22][CH3:23])=[O:21].C(#[N:27])C>C1COCC1>[CH3:23][O:22][C:20](=[O:21])[CH2:19][C:18]([NH:11][C:16]1[CH:15]=[CH:14][C:13]([NH:5][S:2]([CH3:1])(=[O:4])=[O:3])=[CH:12][C:6]=1[S:7](=[O:9])(=[O:8])[NH2:27])=[O:24]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Procedure
In this previously described route to the key intermediate N-(4-methanesulfonylamino-2-sulfamoyl-phenyl)-malonamic acid methyl ester (V) for the production of Setrobuvir, the starting material, 2-amino-5-nitrobenzenesulfonic acid is first converted to the sulfonyl chloride with phosphorus oxychloride, and then quenched with aqueous ammonia, resulting in product (II). Hydrogenation of the nitrosulfonamide product in aqueous ethanol in the presence of methane sulfonic acid using palladium on carbon catalyst provides the mesylate salt of the 2,5-diamino-benzenesulfonamide. This salt is converted to the methanesulfonamide (VIII) with methanesulfonyl chloride and pyridine in acetonitrile. Finally reaction with methyl 3-chloro-3-oxopropanoate in THF provides the key intermediate N-(4-methanesulfonylamino-2-sulfamoyl-phenyl)-malonamic acid methyl ester (V).
Sources & evidence
- ORD record
- ord-6fa25ebf51e242c59ab663a6ec3651cd
- Source dataset
- uspto-grants-2014_08
- Patent number
- US08816120B2
Reaction notes
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