Methanesulfonyl chloride → n-(4-Methanesulfonylamino-2-sulfamoylphenyl)malonamic acid methyl ester

HRID 2410635Notes

Reaction equation

HRID 2410635 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-])=O)=[CH:4][C:3]=1[S:11]([NH2:14])(=[O:13])=[O:12].Cl[C:16](=[O:22])[CH2:17][C:18]([O:20][CH3:21])=[O:19].[H][H].[CH3:25][S:26](Cl)(=[O:28])=[O:27]>C(#N)C.[Pd].C1COCC1.CN(C=O)C.N1C=CC=CC=1>[CH3:21][O:20][C:18](=[O:19])[CH2:17][C:16]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][S:26]([CH3:25])(=[O:28])=[O:27])=[CH:4][C:3]=1[S:11](=[O:13])(=[O:12])[NH2:14])=[O:22]

Participants

9

Reactant 4

HCID 31297Methanesulfonyl chlorideHCID 123460Methyl malonyl chlorideHCID 153583862-Amino-5-nitrobenzenesulfonamideHCID 178418361HCID 178418361, compound

Product 1

HCID 24858399n-(4-Methanesulfonylamino-2-sulfamoylphenyl)malonamic acid methyl ester

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 1049PyridineSolventHCID 6342AcetonitrileSolvent2×HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

In the new route the order of the function group incorporation for the last 3 steps is changed. The first intermediate, 2-amino-5-nitrobenzenesulfonamide (II) is common to both routes. This intermediate is treated with methyl 3-chloro-3-oxopropanoate in acetonitrile. The nitro group is then reduced using hydrogen and palladium on carbon catalyst in a mixture of THF/DMF. Finally mesylation in acetonitrile using methanesulfonyl chloride and pyridine as the base provides the key intermediate N-(4-methanesulfonylamino-2-sulfamoyl-phenyl)-malonamic acid methyl ester (V).

Sources & evidence

ORD record
ord-67e6f02a85884352a2500de9a245d95d
Source dataset
uspto-grants-2014_08
Patent number
US08816120B2

Reaction notes

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