Triethylamine → 1-(3-tert-Butyl-1-(4-cyanophenyl)-1H-pyrazol-5-yl)-3-((5-fluoro-2-(1-(2-hydroxyethyl)-1H-indazole-5-yloxy)phenyl)methyl)urea

HRID 220224Notes

Reaction equation

HRID 220224 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11](=[O:18])OCC(Cl)(Cl)Cl)[N:7]([C:19]2[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH2:26][CH2:27][C:28]1[CH:46]=[C:45]([F:47])[CH:44]=[CH:43][C:29]=1[O:30][C:31]1[CH:32]=[C:33]2[C:37](=[CH:38][CH:39]=1)[N:36]([CH2:40][CH2:41][OH:42])[N:35]=[CH:34]2.C([N:50](CC)CC)C>CC(N(C)C)=O>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:26][CH2:27][C:28]2[CH:46]=[C:45]([F:47])[CH:44]=[CH:43][C:29]=2[O:30][C:31]2[CH:32]=[C:33]3[C:37](=[CH:38][CH:39]=2)[N:36]([CH2:40][CH2:41][OH:42])[N:35]=[CH:34]3)=[O:18])[N:7]([C:19]2[CH:20]=[CH:21][C:22]([C:25]#[N:50])=[CH:23][CH:24]=2)[N:6]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 99310942,2,2-Trichloroethyl 3-tert-butyl-1-P-tolyl-1H-pyrazol-5-ylcarbamateHCID 445421222-(5-(2-(Aminomethyl)-4-fluorophenoxy)-1H-indazol-1-yl)ethanol

Product 1

HCID 687836801-(3-tert-Butyl-1-(4-cyanophenyl)-1H-pyrazol-5-yl)-3-((5-fluoro-2-(1-(2-hydroxyethyl)-1H-indazole-5-yloxy)phenyl)methyl)ureaYield 32.6%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

2,2,2-Trichloroethyl 3-tert-butyl-1-p-tolyl-1H-pyrazol-5-ylcarbamate (0.22 g, 0.529 mmol), 2-(5-(2-(aminomethyl)-4-fluorophenoxy)-1H-indazol-1-yl)ethanol (prepared as in Example 1, Steps E1-E6; 0.175 g, 0.582 mmol), and triethylamine were combined in a minimal amount of DMA and stirred at ambient temperature overnight. The reaction mixture was concentrated, and the residue was diluted with DCM. The DCM was washed with aqueous NH4Cl and aqueous Na2CO3. The organic layer was dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography, eluting with 1% MeOH in ethyl acetate to provide 100 mg (32.6%) of the desired product. MS M+1 (568).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionthe residue was diluted with DCM
  3. washThe DCM was washed with aqueous NH4Cl and aqueous Na2CO3
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with 1% MeOH in ethyl acetate

Sources & evidence

ORD record
ord-8b01769cc7eb4309a298211f140dc960
Source dataset
uspto-grants-2012_06
Patent number
US08202899B2

Reaction notes

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