Diisopropylethylamine → 1-(3-tert-Butyl-1-p-tolyl-1H-pyrazol-5-yl)-3-((2-(1-(2,2-dimethoxyethyl)-1H-indazol-5-yloxy)-5-fluorophenyl)methyl)urea

HRID 1666757Notes

Reaction equation

HRID 1666757 reaction equation
[CH3:1][O:2][CH:3]([O:24][CH3:25])[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=3[CH2:22][NH2:23])=[CH:11][CH:12]=2)[CH:7]=[N:6]1.[C:26]([C:30]1[CH:34]=[C:33]([NH:35][C:36](=O)[O:37]CC(Cl)(Cl)Cl)[N:32]([C:44]2[CH:49]=[CH:48][C:47]([CH3:50])=[CH:46][CH:45]=2)[N:31]=1)([CH3:29])([CH3:28])[CH3:27].C(N(CC)C(C)C)(C)C>CN(C)C(=O)C>[C:26]([C:30]1[CH:34]=[C:33]([NH:35][C:36]([NH:23][CH2:22][C:16]2[CH:17]=[C:18]([F:21])[CH:19]=[CH:20][C:15]=2[O:14][C:10]2[CH:9]=[C:8]3[C:13](=[CH:12][CH:11]=2)[N:5]([CH2:4][CH:3]([O:2][CH3:1])[O:24][CH3:25])[N:6]=[CH:7]3)=[O:37])[N:32]([C:44]2[CH:49]=[CH:48][C:47]([CH3:50])=[CH:46][CH:45]=2)[N:31]=1)([CH3:29])([CH3:28])[CH3:27]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 99310942,2,2-Trichloroethyl 3-tert-butyl-1-P-tolyl-1H-pyrazol-5-ylcarbamateHCID 57552285(2-(1-(2,2-dimethoxyethyl)-1H-indazol-5-yloxy)-5-fluorophenyl)methanamine

Product 1

HCID 575522961-(3-tert-Butyl-1-p-tolyl-1H-pyrazol-5-yl)-3-((2-(1-(2,2-dimethoxyethyl)-1H-indazol-5-yloxy)-5-fluorophenyl)methyl)urea

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
80 °C

Procedure

(2-(1-(2,2-dimethoxyethyl)-1H-indazol-5-yloxy)-5-fluorophenyl)methanamine (2.00 g, 5.791 mmol), 2,2,2-trichloroethyl 3-tert-butyl-1-p-tolyl-1H-pyrazol-5-ylcarbamate (3.516 g, 8.686 mmol) and N,N-diisopropylethylamine (3.026 mL, 17.37 mmol) were suspended in N,N-dimethylacetamide (50 mL) and heated at 80° C. overnight. The reaction mixture was concentrated under reduced pressure and the residue diluted with EtOAc and saturated aqueous NH4Cl. The organics were washed with water (3×), brine, dried (MgSO4) and then concentrated under reduced pressure to afford the crude material, which was purified by flash column chromatography (eluant 35-45% EtOAc/Hexanes). After evaporation of the solvent, the desired product was obtained as a pale yellow foam (2.57 g, 74%). MS (APCI+) m/z 602 (M+1) was detected. 1H NMR (400 MHz, DMSO-d6) δ 7.88 (s, 1H), 7.43 (d, 1H, J=9 Hz), 6.72-7.30 (m, 9H), 6.18 (s, 1H), 6.01 (br, 1H), 5.47 (t, 1H, J=6.1 Hz), 4.76 (t, 1H, J=5.3 Hz), 4.44 (t, 4H, J=5.6 Hz), 3.38 (s, 6H), 2.37 (s, 3H), 1.30 (s, 9H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionthe residue diluted with EtOAc and saturated aqueous NH4Cl
  3. washThe organics were washed with water (3×), brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. customto afford the crude material, which
  7. customwas purified by flash column chromatography (eluant 35-45% EtOAc/Hexanes)
  8. customAfter evaporation of the solvent

Sources & evidence

ORD record
ord-dd82744f10af45fa817dd30506b997ed
Source dataset
uspto-grants-2011_10
Patent number
US08044083B2

Reaction notes

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