Potassium Carbonate → HCID 66937092, compound

HRID 408740Notes

Reaction equation

HRID 408740 reaction equation
[Cl:1][C:2]1[NH:6][C:5]2[CH:7]=[C:8]([Cl:16])[C:9]([O:11][C:12]([F:15])([F:14])[F:13])=[CH:10][C:4]=2[N:3]=1.C([O-])([O-])=O.[K+].[K+].[CH3:23][N:24]([CH3:29])[S:25](Cl)(=[O:27])=[O:26]>CN(C=O)C>[CH3:23][N:24]([CH3:29])[S:25]([N:6]1[C:5]2[CH:7]=[C:8]([Cl:16])[C:9]([O:11][C:12]([F:15])([F:14])[F:13])=[CH:10][C:4]=2[N:3]=[C:2]1[Cl:1])(=[O:27])=[O:26]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 83372Dimethylsulphamoyl chlorideHCID 66937074HCID 66937074, compound

Product 1

HCID 66937092HCID 66937092, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2,6-Dichloro-5-trifluoromethoxy-1H-benzoimidazole (160 g, 0.59 mol, 1.0 equiv.) was dissolved in dry DMF (1.5 L) and then K2CO3 (98 g, 0.71 mol, 1.2 equiv.) and dimethylsulfamoyl chloride (85 g, 0.59 mol, 1.0 equiv.) were added sequentially. The reaction mixture was stirred at room temperature for 16 hours to afford 2,6-dichloro-5-trifluoromethoxy-benzoimidazole-1-sulfonic acid dimethylamide. Without isolation of 2,6-dichloro-5-trifluoromethoxy-benzoimidazole-1-sulfonic acid dimethylamide, 1H-pyrazole-4-carboxylic acid ethyl ester (91 g, 0.65 mol, 1.1 equiv.) and K2CO3 (98 g, 0.71 mol, 1.2 equiv.) were added to the reaction mixture. The reaction mixture was stirred at 70° C. for 10 hours and cooled to room temperature, to afford 1-(6-chloro-1-dimethylsulfamoyl-5-trifluoromethoxy-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid ethyl ester. To crude reaction mixture was added LiOH H2O (124 g, 2.95 mol, 5.0 equiv.) in 2.5 L water. The reaction solution was heated at 70° C. for 6 hours and then cooled to room temperature. Concentrated HCl was added to adjust pH=4.0. The precipitated solid was collected by filtration, washed with water and dried. The solid was recrystallized from hot EtOAc (˜3 L). After cooling to room temperature and filtration, the pure compound was obtained as a white solid (109 g, 0.31 mol, 54% over 3 steps). MS (ESI/CI): mass calcd. for C12H6ClF3N4O2, 346.0; m/z found, 347.0 [M+H]+. 1H NMR (500 MHz, DMSO-d6): 13.79 (s, 1H), 13.06 (s, 1H), 8.91 (s, 1H), 8.33 (s, 1H), 7.79 (br d, 2H).

Sources & evidence

ORD record
ord-633011cebf8e44f4bf66fc421f40ce0e
Source dataset
uspto-grants-2014_06
Patent number
US08759345B2

Reaction notes

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