Potassium Carbonate → HCID 66937490, compound

HRID 538173Notes

Reaction equation

HRID 538173 reaction equation
[CH3:1][N:2]([CH3:22])[S:3]([N:6]1[C:10]2[CH:11]=[C:12]([Cl:20])[C:13]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:14][C:9]=2[N:8]=[C:7]1Cl)(=[O:5])=[O:4].[CH2:23]([O:25][C:26]([C:28]1[CH:29]=[N:30][NH:31][CH:32]=1)=[O:27])[CH3:24].C([O-])([O-])=O.[K+].[K+]>>[CH2:23]([O:25][C:26]([C:28]1[CH:29]=[N:30][N:31]([C:7]2[N:6]([S:3](=[O:5])(=[O:4])[N:2]([CH3:22])[CH3:1])[C:10]3[CH:11]=[C:12]([Cl:20])[C:13]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:14][C:9]=3[N:8]=2)[CH:32]=1)=[O:27])[CH3:24]

Participants

4

Reactant 3

HCID 11430Potassium CarbonateHCID 142179ethyl 1H-pyrazole-4-carboxylateHCID 66937092HCID 66937092, compound

Product 1

HCID 66937490HCID 66937490, compound

Conditions

Temperature
70 °C

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).

Workup

  1. temperaturecooled to room temperature

Sources & evidence

ORD record
ord-041c1a6b54934308ac6de556f8d1a71a
Source dataset
uspto-grants-2014_10
Patent number
US08865713B2

Reaction notes

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