2-(5-(2-(Aminomethyl)-4-fluorophenoxy)-1H-indazol-1-yl)ethanol → 1-((5-fluoro-2-(1-(2-hydroxyethyl)-1H-indazol-5-yloxy)phenyl)methyl)-3-(3-(1-hydroxy-2-methylpropan-2-yl)-1-p-tolyl-1H-pyrazol-5-yl)urea

HRID 220221Notes

Reaction equation

HRID 220221 reaction equation
[OH:1][CH2:2][C:3]([C:6]1[CH:10]=[C:9]([NH:11][C:12](=[O:19])OCC(Cl)(Cl)Cl)[N:8]([C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=2)[N:7]=1)([CH3:5])[CH3:4].[NH2:27][CH2:28][C:29]1[CH:47]=[C:46]([F:48])[CH:45]=[CH:44][C:30]=1[O:31][C:32]1[CH:33]=[C:34]2[C:38](=[CH:39][CH:40]=1)[N:37]([CH2:41][CH2:42][OH:43])[N:36]=[CH:35]2>CC(N(C)C)=O>[F:48][C:46]1[CH:45]=[CH:44][C:30]([O:31][C:32]2[CH:33]=[C:34]3[C:38](=[CH:39][CH:40]=2)[N:37]([CH2:41][CH2:42][OH:43])[N:36]=[CH:35]3)=[C:29]([CH2:28][NH:27][C:12]([NH:11][C:9]2[N:8]([C:20]3[CH:21]=[CH:22][C:23]([CH3:26])=[CH:24][CH:25]=3)[N:7]=[C:6]([C:3]([CH3:5])([CH3:4])[CH2:2][OH:1])[CH:10]=2)=[O:19])[CH:47]=1

Participants

4

Reactant 2

HCID 445421222-(5-(2-(Aminomethyl)-4-fluorophenoxy)-1H-indazol-1-yl)ethanolHCID 445422572,2,2-Trichloroethyl 3-(1-hydroxy-2-methylpropan-2-yl)-1-p-tolyl-1H-pyrazol-5-ylcarbamate

Product 1

HCID 252074011-((5-fluoro-2-(1-(2-hydroxyethyl)-1H-indazol-5-yloxy)phenyl)methyl)-3-(3-(1-hydroxy-2-methylpropan-2-yl)-1-p-tolyl-1H-pyrazol-5-yl)ureaYield 50.9%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

2,2,2-Trichloroethyl 3-(1-hydroxy-2-methylpropan-2-yl)-1-p-tolyl-1H-pyrazol-5-ylcarbamate (0.010 g, 0.024 mmol) was added to a minimal amount of DMA, 2-(5-(2-(Aminomethyl)-4-fluorophenoxy)-1H-indazol-1-yl)ethanol (prepared in steps E1-E6; 0.0079 g, 0.026 mmol) and DEA (0.0084 mmol, 0.048 mmol) were added, and the reaction mixture was stirred at ambient temperature overnight. The reaction mixture was concentrated to remove the majority of DMA. The residue was purified by silica gel chromatography using 5% MeOH in ethyl acetate to provide 7 mg of the title compound. MS M+1 (573).

Workup

  1. additionwere added
  2. concentrationThe reaction mixture was concentrated
  3. customto remove the majority of DMA
  4. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-73515eb8ae274f5584d43f63158bf037
Source dataset
uspto-grants-2012_06
Patent number
US08202899B2

Reaction notes

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