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

HRID 2077458Notes

Reaction equation

HRID 2077458 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]([C:22]([F:25])([F:24])[F:23])=[N:11]2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[CH3:26][N:27]([CH3:40])[CH2:28][CH2:29][O:30][C:31]1[CH:32]=[C:33]([NH2:39])[CH:34]=[CH:35][C:36]=1[O:37][CH3:38].CC([O-:45])(C)C.[Na+].[OH-].[Na+].OO>C1(C)C=CC=CC=1.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]>[CH3:40][N:27]([CH3:26])[CH2:28][CH2:29][O:30][C:31]1[CH:32]=[C:33]([NH:39][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]([C:22]([F:25])([F:24])[F:23])=[N:11]3)[CH:7]=[CH:6][C:3]=2[C:4]([NH2:5])=[O:45])[CH:34]=[CH:35][C:36]=1[O:37][CH3:38]

Participants

9

Reactant 5

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 105603983-(2-(Dimethylamino)ethoxy)-4-methoxyanilineHCID 118541752-bromo-4-[6,6-dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]benzenecarbonitrileHCID 23676156Sodium t-butoxide

Product 1

HCID 118544392-[3-(2-Dimethylamino-ethoxy)-4-methoxy-phenylamino]-4-(6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-indazol-1-yl)-benzamideYield 71%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 1140TolueneSolvent

Procedure

2-bromo-4-(6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-indazol-1-yl)-benzonitrile (500 mg, 1 eq), 3-(2-dimethylamino-ethoxy)-4-methoxy-phenylamine (306 mg, 1.2 eq), Pd(OAc)2 (14 mg), DPPF (66 mg), and NaOtBu (214 mg, 2 eq) were mixed in toluene (5 mL) and microwaved at 140° C. for 25 minutes. Then 10 mL of EtOH(4)/H2O(1) were added, followed by NaOH (700 mg, 2 eq) and H2O2 (1 mL). The mixture was microwaved at 100° C. for 15 min, then concentrated to dryness, and purified by flash chromatography, eluting with 20% EtOH in dichloromethane to give the title compound (480 mg, 71% two-step yield). LCMS (m/z): M+H=560.3.

Workup

  1. custommicrowaved at 140° C. for 25 minutes
  2. customThe mixture was microwaved at 100° C. for 15 min
  3. concentrationconcentrated to dryness
  4. custompurified by flash chromatography
  5. washeluting with 20% EtOH in dichloromethane

Sources & evidence

ORD record
ord-88c59da88324469992fe0bf13d6c994a
Source dataset
uspto-grants-2011_04
Patent number
US07928135B2

Reaction notes

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