4-Chlorobenzenesulfonyl chloride → Methyl 2-(3-chloro-4-(6-(4-chlorophenylsulfonamido)-1,3-dioxoisoindolin-5-yloxy)phenyl)acetate

HRID 2423324Notes

Reaction equation

HRID 2423324 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6](=[O:12])[NH:7][C:8]2=[O:11])=[CH:4][C:3]=1[O:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][C:21]([O:23][CH3:24])=[O:22])=[CH:16][C:15]=1[Cl:25].[Cl:26][C:27]1[CH:32]=[CH:31][C:30]([S:33](Cl)(=[O:35])=[O:34])=[CH:29][CH:28]=1.N1C(C)=CC=CC=1C>ClCCl>[Cl:25][C:15]1[CH:16]=[C:17]([CH2:20][C:21]([O:23][CH3:24])=[O:22])[CH:18]=[CH:19][C:14]=1[O:13][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:2]=1[NH:1][S:33]([C:30]1[CH:31]=[CH:32][C:27]([Cl:26])=[CH:28][CH:29]=1)(=[O:35])=[O:34])[C:8](=[O:11])[NH:7][C:6]2=[O:12]

Participants

5

Reactant 3

HCID 73984-Chlorobenzenesulfonyl chlorideHCID 79372,6-LutidineHCID 59864779Methyl 2-(4-(6-amino-1,3-dioxoisoindolin-5-yloxy)-3-chlorophenyl)acetate

Product 1

HCID 67244284Methyl 2-(3-chloro-4-(6-(4-chlorophenylsulfonamido)-1,3-dioxoisoindolin-5-yloxy)phenyl)acetate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Compound 30.2 (25 mg, 0.07 mmol) and 4-chlorobenzenesulfonyl chloride (30 mg, 0.14 mmol) were stirred in dichloromethane (0.5 mL) with 2,6-lutidine (0.25 mL, 0.21 mmol) at 25° C. for 14 h. The reaction mixture was loaded directly on a silica gel column and purified using 20% EtOAc/hexane as the eluent to give methyl 2-(3-chloro-4-(6-(4-chlorophenylsulfonamido)-1,3-dioxoisoindolin-5-yloxy)phenyl)acetate, and a compound with LC-MS matching a bis-sulfonamide. Both acetates were hydrolyzed in MeOH/THF/water (0.3 mL each) with LiOH.H2O (6 mg, 0.14 mmol) at 25° C. for 2 h to give the same desired product (30). The reaction mixtures were acidified to pH ˜3 and extracted with dichloromethane to give compound 30 as a pale-yellow solid. MS ESI (pos.) m/e calcd for (M+H3O)+ 539.0. found 539.0. 1H NMR (500 MHz) (DMSO-d6) δ 12.46 (br. s, 1H); 10.42 (s, 1H); 7.79 (d, J=8.3 Hz, 2H); 7.64 (d, J=8.5 Hz, 2H); 7.50 (d, J=1.9 Hz, 1H); 7.24 (dd, J=11.9, 8.3 Hz, 1H); 7.18 (s, 1H); 7.08 (s, 1H); 6.98 (s, 1H); 6.81 (d, J=8.2 Hz, 1H); 3.64 (s, 2H).

Workup

  1. custompurified

Sources & evidence

ORD record
ord-eebafd453c664d14b171fb4e7ef431d6
Source dataset
uspto-grants-2011_06
Patent number
US07960567B2

Reaction notes

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