Hydrogen Peroxide → 2-[3-(2-Dimethylamino-ethoxy)-4-methoxy-phenylamino]-4-(3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-indazol-1-yl)-benzamide

HRID 1875404Notes

Reaction equation

HRID 1875404 reaction equation
Br[C:2]1[CH:9]=[C:8]([N:10]2[C:18]3[CH2:17][C:16]([CH3:20])([CH3:19])[CH2:15][C:14](=[O:21])[C:13]=3[C:12]([CH3:22])=[N:11]2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].CC([O-:27])(C)C.[Na+].[CH3:29][N:30]([CH3:43])[CH2:31][CH2:32][O:33][C:34]1[CH:35]=[C:36]([NH2:42])[CH:37]=[CH:38][C:39]=1[O:40][CH3:41].[OH-].[Na+].OO>C(O)C.CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].CS(C)=O.C1(C)C=CC=CC=1>[CH3:43][N:30]([CH3:29])[CH2:31][CH2:32][O:33][C:34]1[CH:35]=[C:36]([NH:42][C:2]2[CH:9]=[C:8]([N:10]3[C:18]4[CH2:17][C:16]([CH3:20])([CH3:19])[CH2:15][C:14](=[O:21])[C:13]=4[C:12]([CH3:22])=[N:11]3)[CH:7]=[CH:6][C:3]=2[C:4]([NH2:5])=[O:27])[CH:37]=[CH:38][C:39]=1[O:40][CH3:41]

Participants

11

Reactant 5

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 105603983-(2-(Dimethylamino)ethoxy)-4-methoxyanilineHCID 118541702-Bromo-4-(3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indazol-1-yl)benzonitrileHCID 23676156Sodium t-butoxide

Product 1

HCID 118546872-[3-(2-Dimethylamino-ethoxy)-4-methoxy-phenylamino]-4-(3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-indazol-1-yl)-benzamide

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 679Dimethyl SulfoxideSolventHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
130 °C

Procedure

2-Bromo-4-(6,6-dimethyl-4-oxo-3-methyl-4,5,6,7-tetrahydro-indazol-1-yl)-benzonitrile (100 mg, 0.28 mmol), Pd(OAc)2 (3.1 mg, 5 mol %), DPPF (15.5 mg, 10 mol %) and NaOtBu (52 mg, 0.56 mmol) were added to a microwave vial. Toluene (0.5 mL) and 3-(2-dimethylamino-ethoxy)-4-methoxy-phenylamine (118 mg, 2 mol eq) were added and the vial was evacuated and back-filled with N2. The reaction mixture was heated at 130° C. for 30 min (microwave). The reaction mixture was filtered and the solids washed with CH2Cl2. The product nitrile was purified using flash chromatography eluting with CH2Cl2 and methanol. This nitrile (32 mg, 0.66 mmol) was dissolved in ethanol (0.8 mL) and DMSO (0.2 mL) to which NaOH (5 N, 26 μL, 2 eq) and H2O2 (excess, 30% solution in H2O) was added. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was washed with H2O and extracted with EtOAc. The product was purified using flash chromatography eluting with CH2Cl2 and methanol. The title compound was obtained as a yellow solid (10 mg, 30%); LC/MS (m/z): M+H=506.5.

Workup

  1. customthe vial was evacuated
  2. additionback-filled with N2
  3. filtrationThe reaction mixture was filtered
  4. washthe solids washed with CH2Cl2
  5. customThe product nitrile was purified
  6. washeluting with CH2Cl2 and methanol
  7. washThe reaction mixture was washed with H2O
  8. extractionextracted with EtOAc
  9. customThe product was purified
  10. washeluting with CH2Cl2 and methanol

Sources & evidence

ORD record
ord-8e261a0098ed42c6aaaeb25737fb296c
Source dataset
uspto-grants-2012_11
Patent number
US08309548B2

Reaction notes

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