Water → 4-{[3-(5-Amino-1H-pyrazol-4-yl)-3'-cyanobiphenyl-4-yl]oxy}-5-chloro-2-fluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide

HRID 1619613Notes

Reaction equation

HRID 1619613 reaction equation
[Cl:1][C:2]1[C:3]([O:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([C:31]#[N:32])[CH:26]=3)=[CH:21][C:20]=2[C:33]2[C:34]([N+:38]([O-])=O)=[N:35][NH:36][CH:37]=2)=[CH:4][C:5]([F:17])=[C:6]([S:8]([NH:11][C:12]2[S:13][CH:14]=[N:15][N:16]=2)(=[O:10])=[O:9])[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].S(S([O-])=O)([O-])=O.[Na+].[Na+].O>C(#N)C>[NH2:38][C:34]1[NH:35][N:36]=[CH:37][C:33]=1[C:20]1[CH:21]=[C:22]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]#[N:32])[CH:26]=2)[CH:23]=[CH:24][C:19]=1[O:18][C:3]1[C:2]([Cl:1])=[CH:7][C:6]([S:8]([NH:11][C:12]2[S:13][CH:14]=[N:15][N:16]=2)(=[O:9])=[O:10])=[C:5]([F:17])[CH:4]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 24489Sodium DithioniteHCID 178509691HCID 178509691, compound

Product 1

HCID 566017824-{[3-(5-Amino-1H-pyrazol-4-yl)-3'-cyanobiphenyl-4-yl]oxy}-5-chloro-2-fluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

5-Chloro-4-(3′-cyano-3-(3-nitro-1H-pyrazol-4-yl)biphenyl-4-yloxy)-2-fluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide (Preparation 62, 51 mg, 0.0853 mmol) was dissolved in acetonitrile (1 mL) and heated at 50° C. Potassium carbonate (58.8 mg, 0.426 mmol) followed by sodium dithionite (59.4 mg, 0.341 mmol) and water (1 mL) were added. The reaction mixture was heated at 50° C. for 2 hours, cooled to room temperature and partitioned between EtOAc (10 mL) and water (5 mL). The aqueous phase was separated and extracted with EtOAc (2×3 mL) and the combined organic phases were washed with a saturated solution of brine (3 mL), dried over MgSO4 and concentrated in vacuo. The crude residue was purified by reverse phase HPLC.

Workup

  1. additionwere added
  2. temperatureThe reaction mixture was heated at 50° C. for 2 hours
  3. temperaturecooled to room temperature
  4. custompartitioned between EtOAc (10 mL) and water (5 mL)
  5. customThe aqueous phase was separated
  6. extractionextracted with EtOAc (2×3 mL)
  7. washthe combined organic phases were washed with a saturated solution of brine (3 mL)
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo
  10. customThe crude residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-eb3cea3331094a5287d5d4bc142cc226
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

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