Potassium Carbonate → 3-Cyano-4-[(3-Pyridazin-4-ylbiphenyl-4-yl)oxy]-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide

HRID 1619593Notes

Reaction equation

HRID 1619593 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[CH:8]=[C:9]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:10]=[CH:11][C:12]=2[OH:13])=[CH:3][N:2]=1.[C:20]([C:22]1[CH:23]=[C:24]([S:29]([N:32](CC2C=CC(OC)=CC=2OC)[C:33]2[S:34][CH:35]=[N:36][N:37]=2)(=[O:31])=[O:30])[CH:25]=[CH:26][C:27]=1F)#[N:21].C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[C:20]([C:22]1[CH:23]=[C:24]([S:29]([NH:32][C:33]2[S:34][CH:35]=[N:36][N:37]=2)(=[O:31])=[O:30])[CH:25]=[CH:26][C:27]=1[O:13][C:12]1[CH:11]=[CH:10][C:9]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:8][C:7]=1[C:4]1[CH:5]=[CH:6][N:1]=[N:2][CH:3]=1)#[N:21]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 580422813-cyano-N-(2,4-dimethoxybenzyl)-4-fluoro-N-1,3,4-thiadiazol-2-ylbenzenesulfonamideHCID 1362008863-Pyridazin-4-ylbiphenyl-4-ol

Product 1

HCID 566007913-Cyano-4-[(3-Pyridazin-4-ylbiphenyl-4-yl)oxy]-N-1,3,4-thiadiazol-2-ylbenzenesulfonamideYield 24.4%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

3-Pyridazin-4-ylbiphenyl-4-ol (Preparation 4, 50 mg, 0.2 mmol) and 3-cyano-N-(2,4-dimethoxybenzyl)-4-fluoro-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide (Preparation 15, 87.3 mg, 0.2 mmol) were dissolved in dimethylsulfoxide (2 mL). Potassium carbonate (83 mg, 0.6 mmol) was added and the reaction stirred at room temperature for 16 hours. The crude material was partitioned between ethyl acetate (20 mL) and water (20 mL), the organic layer separated, concentrated in vacuo, dissolved in trifluoroacetic acid (1 mL) and the solution stirred for 16 hours at room temperature. The reaction was concentrated in vacuo then purified by reverse phase column chromatography (ISCO™, 12 g, C18, 20:1 water:acetonitrile to 1:4 water:acetonitrile). The appropriate fractions were combined and concentrated in vacuo to afford the title compound as a white solid (25 mg, 24%).

Workup

  1. customThe crude material was partitioned between ethyl acetate (20 mL) and water (20 mL)
  2. customthe organic layer separated
  3. concentrationconcentrated in vacuo
  4. dissolutiondissolved in trifluoroacetic acid (1 mL)
  5. stirringthe solution stirred for 16 hours at room temperature
  6. concentrationThe reaction was concentrated in vacuo
  7. customthen purified by reverse phase column chromatography (ISCO™, 12 g, C18, 20:1 water:acetonitrile to 1:4 water:acetonitrile)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fc75942666ec4f3686c57bad8f5db49b
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

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