Ethanol → 5-(4-Amino-2-fluorophenoxy)-N-benzhydryl-1-methyl-1H-indazol-6-amine

HRID 2195503Notes

Reaction equation

HRID 2195503 reaction equation
[C:1]1([C:7]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[N:8][C:9]2[CH:17]=[C:16]3[C:12]([CH:13]=[N:14][N:15]3[CH3:18])=[CH:11][C:10]=2[O:19][C:20]2[CH:25]=[CH:24][C:23]([N+:26]([O-])=O)=[CH:22][C:21]=2[F:29])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCO.C([O-])=O.[NH4+]>[Pd].CCOC(C)=O>[NH2:26][C:23]1[CH:24]=[CH:25][C:20]([O:19][C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][C:9]=2[NH:8][CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[N:15]([CH3:18])[N:14]=[CH:13]3)=[C:21]([F:29])[CH:22]=1

Participants

6

Reactant 3

HCID 702EthanolHCID 2723923Ammonium formateHCID 86638473N-(Diphenylmethylene)-5-(2-fluoro-4-nitrophenoxy)-1-methyl-1H-indazol-6-amine

Product 1

HCID 667671865-(4-Amino-2-fluorophenoxy)-N-benzhydryl-1-methyl-1H-indazol-6-amineYield 51.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a 100 mL round bottom flask is added N-(diphenylmethylene)-5-(2-fluoro-4-nitrophenoxy)-1-methyl-1H-indazol-6-amine (424 mg, 909 μmol) and EtOH (35 mL, 601 mmol). To the mixture is added ammonium formate (1000 mg, 15.9 mmol) followed by the addition of 10% Pd/C (300 mg, 141 μmol) and the reaction mixture is stirred at RT for 1 hour and heated at 45° C. for 15 min. The solvent is removed and the residue is dissolved in DCM (150 mL) and distilled water (100 mL). The organic layer is washed with distilled water (1 x 100 mL), and the combined aqueous layers are extracted with DCM (1 x 50 mL). The combined organic solution is dried with Na2SO4, filtered, and concentrated. The crude is purified on a silica gel column eluting with hexanes (A) and EtOAc (B), gradient from 90% (A)10% (B) to 40% (A):60% (B) over 90 min to give an off-white solid material as the title compound (204 mg, 51% yield). MS (m/z): 438.8 (M+H).

Workup

  1. temperatureheated at 45° C. for 15 min
  2. customThe solvent is removed
  3. dissolutionthe residue is dissolved in DCM (150 mL)
  4. distillationdistilled water (100 mL)
  5. washThe organic layer is washed with distilled water (1 x 100 mL)
  6. extractionthe combined aqueous layers are extracted with DCM (1 x 50 mL)
  7. dry with materialThe combined organic solution is dried with Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude is purified on a silica gel column
  11. washeluting with hexanes (A) and EtOAc (B), gradient from 90% (A)10% (B) to 40% (A)

Sources & evidence

ORD record
ord-b276731e8c95491b959f53571448bfd8
Source dataset
uspto-grants-2012_12
Patent number
USRE043878E1

Reaction notes

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