Diethyl Malonate → N-(4-methanesulfonylamino-2-sulfamoyl-phenyl)-malonamic acid ethyl ester
Reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][S:9]([CH3:12])(=[O:11])=[O:10])=[CH:4][C:3]=1[S:13]([NH2:16])(=[O:15])=[O:14].[C:17](OCC)(=[O:24])[CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20]>>[CH2:22]([O:21][C:19](=[O:20])[CH2:18][C:17]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][S:9]([CH3:12])(=[O:10])=[O:11])=[CH:4][C:3]=1[S:13](=[O:14])(=[O:15])[NH2:16])=[O:24])[CH3:23]Participants
Conditions
- Temperature
- 160 °C
Procedure
To 2-amino-5-methanesulfonylamino-benzenesulfonamide (Example 17d, 175 mg, 0.66 mmol) was added diethyl malonate (297 mg, 1.66 mmol) and heated at 160° C. for 60 min. After cooling down to 25° C., a 1:1 mixture of ethyl acetate/hexanes (5 mL) was added, upon which as a white solid precipitated out. The solid was collected by vacuum filtration, washed twice with a 1:1 mixture of ethyl acetate/hexanes, and dried under high vacuum to afford the desired product, N-(4-methanesulfonylamino-2-sulfamoyl-phenyl)-malonamic acid ethyl ester (179 mg, 0.47 mmol, 72% yield) as an off-white solid. 1H NMR (400 MHz, CD3OD) δ: 1.32 (t, 3H, J=7.0 Hz), 3.00 (s, 3H), 3.60 (s, 2H), 4.25 (quartet, 2H, J=6.8 Hz), 7.44 (dd, 1H, J1=3.2 Hz, J2=8.4 Hz), 7.87 (d, 1H, J=5.6 Hz), 7.92 (d, 1H, J=8.4 Hz). LC-MS (ESI+) calcd for C12H17N3O7S2 379.05, found 380.1 [M+H+].
Workup
- temperatureAfter cooling down to 25° C.
- additionwas added, upon which as a white solid
- customprecipitated out
- filtrationThe solid was collected by vacuum filtration
- washwashed twice with a 1:1 mixture of ethyl acetate/hexanes
- customdried under high vacuum
Sources & evidence
- ORD record
- ord-5f27106fd17b4f07a12beffba99760e9
- Source dataset
- uspto-grants-2009_09
- Patent number
- US07582754B2
Reaction notes
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