Ammonium Chloride → HCID 178509252, compound

HRID 46264Notes

Reaction equation

HRID 46264 reaction equation
[Cl:1][C:2]1[C:3]([O:29][C:30]2[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][C:31]=2[C:40]2[C:41]([N+:51]([O-])=O)=[N:42][N:43](C3CCCCO3)[CH:44]=2)=[CH:4][C:5]([F:28])=[C:6]([S:8]([N:11](CC2C=CC(OC)=CC=2OC)[C:12]2[S:13][CH:14]=[N:15][N:16]=2)(=[O:10])=[O:9])[CH:7]=1.[Cl-].[NH4+]>C(O)C.[Fe]>[NH2:51][C:41]1[C:40]([C:31]2[CH:32]=[C:33]([C:36]([F:37])([F:39])[F:38])[CH:34]=[CH:35][C:30]=2[O:29][C:3]2[C:2]([Cl:1])=[CH:7][C:6]([S:8]([NH:11][C:12]3[S:13][CH:14]=[N:15][N:16]=3)(=[O:10])=[O:9])=[C:5]([F:28])[CH:4]=2)=[CH:44][NH:43][N:42]=1

Participants

5

Reactant 2

HCID 25517Ammonium ChlorideHCID 669058755-chloro-N-(2,4-dimethoxybenzyl)-2-fluoro-4-{2-[3-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-4-(trifluoromethyl)phenoxy}-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide

Product 1

HCID 178509252HCID 178509252, compound

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 5-chloro-N-(2,4-dimethoxybenzyl)-2-fluoro-4-{2-[3-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-4-(trifluoromethyl)phenoxy}-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide (Preparation 867, 3.20 g, 4.00 mmol) in ethanol (200 mL) was added saturated aqueous ammonium chloride solution (50 mL) and iron (5.66 g, 101 mmol). The reaction solution was heated at 80° C. for 15 minutes. The solution was cooled, filtered and adjusted to pH=9 with saturated aqueous sodium bicarbonate solution. The mixture was filtered and then concentrated to remove most of the ethanol. The resulting slurry was extracted with dichloromethane (3×). The organic extracts were combined, dried over anhydrous magnesium sulfate, filtered, and concentrated. This provided the aminopyrazole as a yellow foam. To this was added an HCl (g) saturated methanol solution (200 mL) and the mixture heated at 60° C. for two hours. The reaction solution was cooled, concentrated, and purified by automated flash column chromatography using a 0-10% methanol/dichloromethane gradient. Additional purification by prep HPLC provided the TFA salt. The resulting white solid was redissolved in a HCl (g) saturated methanol solution and concentrated (3×) in order to isolate the HCl salt of the title compound (1.20 g, 53%) as a white solid.

Workup

  1. temperatureThe solution was cooled
  2. filtrationfiltered
  3. filtrationThe mixture was filtered
  4. concentrationconcentrated
  5. customto remove most of the ethanol
  6. extractionThe resulting slurry was extracted with dichloromethane (3×)
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-a56b2fb34d9b4a5b801b4d1e1d9caa42
Source dataset
uspto-grants-2013_09
Patent number
US08541588B2

Reaction notes

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