Potassium Carbonate → [5-(5-Amino-3-tert-butyl-pyrazol-1-yl)-2-triisopropylsilanyloxy-phenyl]-methanol

HRID 60654

Reaction equation

HRID 60654 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH2:10])[NH:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].I[C:12]1[CH:13]=[CH:14][C:15]([O:20][Si:21]([CH:28]([CH3:30])[CH3:29])([CH:25]([CH3:27])[CH3:26])[CH:22]([CH3:24])[CH3:23])=[C:16]([CH2:18][OH:19])[CH:17]=1.C(=O)([O-])[O-].[K+].[K+].CN[C@H]1CCCC[C@@H]1NC>C1(C)C=CC=CC=1.CCOC(C)=O.O.[Cu]I>[NH2:10][C:8]1[N:7]([C:12]2[CH:13]=[CH:14][C:15]([O:20][Si:21]([CH:25]([CH3:27])[CH3:26])([CH:28]([CH3:30])[CH3:29])[CH:22]([CH3:23])[CH3:24])=[C:16]([CH2:18][OH:19])[CH:17]=2)[N:6]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[CH:9]=1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 13822957(1S,2S)-(+)-N,N'-Dimethylcyclohexane-1,2-diamineHCID 123603074(5-Iodo-2-triisopropylsilanyloxy-phenyl)-methanolHCID 178441179HCID 178441179, compound

Product 1

HCID 123490636[5-(5-Amino-3-tert-butyl-pyrazol-1-yl)-2-triisopropylsilanyloxy-phenyl]-methanolYield 15%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

3-(Tert-butyl)-1H-pyrazol-5-amine (0.32 g, 2.30 mmol) was treated with a solution of Intermediate 61b (1.04 g, 2.60 mmol) in toluene (4 mL) then potassium carbonate (0.68 g, 4.90 mmol), (1S,2S)—N,N′-bis-methyl-1,2-cyclohexane-diamine (0.07 g, 0.47 mmol) and copper (I) iodide (0.022 g, 0.11 mmol) were added. The mixture was degassed then heated at 150° C. for 1 h using microwave irradiation. Another portion of copper (I) iodide (0.022 g, 0.11 mmol) was added and the reaction mixture heated at 150° C. for a further 1 h using microwave irradiation. The mixture was diluted with EtOAc and water and the phases separated. The aqueous layer was then extracted with EtOAc (2×). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo. The organic layer was evaporated in vacuo. The residue was purified by FCC, using 0-15% EtOAc in DCM, to give the title compound (0.14 g, 15%). LCMS (Method 3): Rt 3.87 min, m/z 418 [MH+].

Workup

  1. customThe mixture was degassed
  2. custommicrowave irradiation
  3. temperaturethe reaction mixture heated at 150° C. for a further 1 h
  4. custommicrowave irradiation
  5. customthe phases separated
  6. extractionThe aqueous layer was then extracted with EtOAc (2×)
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. customThe organic layer was evaporated in vacuo
  12. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-7dce753c8f5c45a68a5441a0e32fa862
Source dataset
uspto-grants-2016_09
Patent number
US09440974B2

Linked notes

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