Aniline → HCID 59494858, compound

HRID 872044Notes

Reaction equation

HRID 872044 reaction equation
Br[C:2]1[C:10]2[C:5](=[CH:6][C:7]([CH2:11][N:12]([CH:20]3[CH2:22][CH2:21]3)[C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[CH:8][CH:9]=2)[N:4]([CH2:23][CH2:24][CH2:25][O:26][CH3:27])[N:3]=1.[NH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[K+].[K+]>C(O)(C)(C)C.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].O>[NH:28]([C:2]1[C:10]2[C:5](=[CH:6][C:7]([CH2:11][N:12]([CH:20]3[CH2:22][CH2:21]3)[C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[CH:8][CH:9]=2)[N:4]([CH2:23][CH2:24][CH2:25][O:26][CH3:27])[N:3]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

8

Reactant 4

HCID 6115AnilineHCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 59494314HCID 59494314, compound

Product 1

HCID 59494858HCID 59494858, compoundYield 78.8%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of tert-butyl {[3-bromo-1-(3-methoxypropyl)-1H-indazol-6-yl]methyl}cyclopropylcarbamate (200 mg), aniline (64 mg), 2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl (X-Phos) (8.7 ml), potassium carbonate (88 mg) and tris(dibenzylideneacetone)dipalladium (4.2 mg) in tert-butanol (3 ml) was stirred at 100° C. for 24 hours under argon atmosphere. Water was added to the reaction mixture under ice-cooling and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over sodium sulfate and concentrated in vacuo. The resulted residue was purified with a silica gel column chromatography (eluting solvent: n-hexane to n-hexane/ethyl acetate=2/1) to give tert-butyl {[3-anilino-1-(3-methoxypropyl)-1H-indazol-6-yl]methyl}cyclopropylcarbamate (162 mg) as a yellow oil.

Workup

  1. temperaturecooling
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe resulted residue was purified with a silica gel column chromatography (eluting solvent: n-hexane to n-hexane/ethyl acetate=2/1)

Sources & evidence

ORD record
ord-b9807ee295964b398f32b53801e03504
Source dataset
uspto-grants-2015_03
Patent number
US08975252B2

Reaction notes

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