Potassium Carbonate → 3-Cyano-N-(2,4-dimethoxybenzyl)-4-{[2-pyridazin-4-yl-4-(trifluoromethyl)phenyl]thio}-N-1,2,4-thiadiazol-5ylbenzenesulfonamide

HRID 509111Notes

Reaction equation

HRID 509111 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[C:12]1[CH:17]=[CH:16][N:15]=[N:14][CH:13]=1.C([Si](C(C)C)(C(C)C)[SH:22])(C)C.C(=O)([O-])[O-].[K+].[K+].[C:35]([C:37]1[CH:38]=[C:39]([S:44]([N:47]([CH2:53][C:54]2[CH:59]=[CH:58][C:57]([O:60][CH3:61])=[CH:56][C:55]=2[O:62][CH3:63])[C:48]2[S:52][N:51]=[CH:50][N:49]=2)(=[O:46])=[O:45])[CH:40]=[CH:41][C:42]=1F)#[N:36]>CN(C)C(=O)C.C(OCC)(=O)C>[C:35]([C:37]1[CH:38]=[C:39]([S:44]([N:47]([CH2:53][C:54]2[CH:59]=[CH:58][C:57]([O:60][CH3:61])=[CH:56][C:55]=2[O:62][CH3:63])[C:48]2[S:52][N:51]=[CH:50][N:49]=2)(=[O:46])=[O:45])[CH:40]=[CH:41][C:42]=1[S:22][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[C:12]1[CH:17]=[CH:16][N:15]=[N:14][CH:13]=1)#[N:36]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 3435097Tris(propan-2-yl)silanethiolHCID 580422543-cyano-N-(2,4-dimethoxybenzyl)-4-fluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamideHCID 666528604-[2-Chloro-5-(trifluoromethyl)phenyl]pyridazine

Product 1

HCID 666524503-Cyano-N-(2,4-dimethoxybenzyl)-4-{[2-pyridazin-4-yl-4-(trifluoromethyl)phenyl]thio}-N-1,2,4-thiadiazol-5ylbenzenesulfonamideYield 73.4%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
130 °C

Procedure

4-[2-Chloro-5-(trifluoromethyl)phenyl]pyridazine (Preparation 21, 0.050 g, 0.193 mmol), triisopropylsilanethiol (0.090 g, 472 mmol) and potassium carbonate (0.055 g, 0.398 mmol) were dissolved in N,N-dimethylacetamide (2 mL) in a Reactivial®. The reaction mixture was heated to 130° C. for 1 hour and 15 minutes. Then, the reaction was cooled to room temperature and 3-cyano-N-(2,4-dimethoxybenzyl)-4-fluoro-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide (Preparation 1, 0.085 g, 1.96 mmol) was added. The mixture was stirred at room temperature for thirty minutes. The reaction mixture was diluted in ethyl acetate (15 mL) and washed twice with a solution of saturated aqueous brine (15 mL). The aqueous layer was extracted with ethyl acetate (5 mL). The organic phases were combined and dried over sodium sulphate, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (ISCO™, 0-50% ethyl acetate in heptane gradient elution, 12 g SiO2) to give title compound as a yellow foam (0.095 g, 73%).

Workup

  1. temperatureThen, the reaction was cooled to room temperature
  2. washwashed twice with a solution of saturated aqueous brine (15 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (5 mL)
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography (ISCO™, 0-50% ethyl acetate in heptane gradient elution, 12 g SiO2)

Sources & evidence

ORD record
ord-8d56da44f8f746a4bd2129f181d3b645
Source dataset
uspto-grants-2015_08
Patent number
US09096558B2

Reaction notes

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