Toluene → N-(Diphenylmethylene)-5-(2-fluoro-4-nitrophenoxy)-1-methyl-1H-indazol-6-amine

HRID 1661986Notes

Reaction equation

HRID 1661986 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH3:11])=[CH:4][C:3]=1[O:12][C:13]1[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][C:14]=1[F:22].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C1(C)C=CC=CC=1.[C:72](=[NH:85])([C:79]1[CH:84]=[CH:83][CH:82]=[CH:81][CH:80]=1)[C:73]1[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=1.CC(C)([O-])C.[Na+]>C(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CCOC(C)=O>[C:79]1([C:72]([C:73]2[CH:74]=[CH:75][CH:76]=[CH:77][CH:78]=2)=[N:85][C:2]2[CH:10]=[C:9]3[C:5]([CH:6]=[N:7][N:8]3[CH3:11])=[CH:4][C:3]=2[O:12][C:13]2[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][C:14]=2[F:22])[CH:80]=[CH:81][CH:82]=[CH:83][CH:84]=1

Participants

9

Reactant 5

HCID 1140TolueneHCID 136809Benzophenone imineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 667668536-Bromo-5-(2-fluoro-4-nitrophenoxy)-1-methyl-1H-indazole

Product 1

HCID 86638473N-(Diphenylmethylene)-5-(2-fluoro-4-nitrophenoxy)-1-methyl-1H-indazol-6-amineYield 90.1%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
150 °C

Procedure

To a 10 mL microwave vial is added 6-bromo-5-(2-fluoro-4-nitrophenoxy)-1-methyl-1H-indazole (500 mg, 1.37 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (73 mg, 123 μmol) and Pd2(dba)3 (38 mg, 41 μmol). The mixture is suspended in toluene (5 mL, 47 mmol) and benzophenone imine (272 mg, 1.5 mmol) and sodium tert-butoxide (203 mg, 2.05 mmol) are added. The mixture is heated at 150° C. for 20 min in a microwave reactor. After cooling, the reaction solution is concentrated to give a brown oil which is dissolved in DCM (150 mL) and washed with saturated aqueous sodium chloride (2×50 mL). The aqueous layers are combined and extracted with DCM (1×50 mL), dried with Na2SO4, filtered and concentrated to give a brown residue. The residue is purified on a silica gel column eluting with hexanes (A) and EtOAc (B), gradient from 85%(A): 15%(B) to 50%(A):50%(B) over 50 min to give a yellow solid material as the title compound (574 mg, 90.1% yield). MS (m/z): 467.2 (M+H).

Workup

  1. temperatureAfter cooling
  2. concentrationthe reaction solution is concentrated
  3. customto give a brown oil which
  4. washwashed with saturated aqueous sodium chloride (2×50 mL)
  5. extractionextracted with DCM (1×50 mL)
  6. dry with materialdried with Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a brown residue
  10. customThe residue is purified on a silica gel column
  11. washeluting with hexanes (A) and EtOAc (B), gradient from 85%(A)

Sources & evidence

ORD record
ord-820e8cd2cbc7439fa57691c980fac8fd
Source dataset
uspto-grants-2011_10
Patent number
US08030302B2

Reaction notes

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