Potassium Carbonate → {5-Amino-3-tert-butyl-1'-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1'H-[1,4']bipyrazolyl-3'-yl}-methanol

HRID 60676

Reaktionsgleichung

Reaktionsgleichung von HRID 60676
I[C:2]1[C:3]([CH2:16][OH:17])=[N:4][N:5]([CH2:7][CH2:8][O:9][CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][O:11]2)[CH:6]=1.[C:18]([C:22]1[CH:26]=[C:25]([NH2:27])[NH:24][N:23]=1)([CH3:21])([CH3:20])[CH3:19].C(=O)([O-])[O-].[K+].[K+].CN[C@@H]1CCCC[C@H]1NC>C1(C)C(C)=CC=CC=1.O.[OH-].[NH4+].CCOC(C)=O.[Cu]I>[NH2:27][C:25]1[N:24]([C:2]2[C:3]([CH2:16][OH:17])=[N:4][N:5]([CH2:7][CH2:8][O:9][CH:10]3[CH2:15][CH2:14][CH2:13][CH2:12][O:11]3)[CH:6]=2)[N:23]=[C:22]([C:18]([CH3:21])([CH3:20])[CH3:19])[CH:26]=1

Komponenten

10

Edukt 4

HCID 11430Potassium CarbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 117729333HCID 117729333, VerbindungHCID 178441179HCID 178441179, Verbindung

Produkt 1

HCID 117729489{5-Amino-3-tert-butyl-1'-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1'H-[1,4']bipyrazolyl-3'-yl}-methanolAusbeute 63 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Katalysator2×HCID 962WaterLösungsmittelHCID 7237O-XyleneLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 14923Ammonium HydroxideLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

A solution of Intermediate 74d (0.51 g, 1.45 mmol) in xylene (2.4 mL) was treated with 3-(tert-butyl)-1H-pyrazol-5-amine (0.18 g, 1.32 mmol) then potassium carbonate (0.38 g, 2.76 mmol), trans-N,N′-Dimethyl-1,2-cyclohexanediamine (0.037 g, 0.26 mmol) and copper (I) iodide (0.013 g, 0.066 mmol) were added. The mixture was degassed then heated at 150° C. for 4 h using microwave irradiation. Another portion of copper (I) iodide (0.006 g, 0.03 mmol) was added and the reaction mixture heated at 150° C. for a further 2 h using microwave irradiation. The mixture was diluted with water (1 mL), conc. aqueous ammonium hydroxide (1 mL) and EtOAc (1 mL) and the phases separated. The aqueous layer was then extracted with EtOAc (2×). The combined organic layers were washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by FCC, using 0-5% MeOH in DCM to give the title compound as a dark green gum (0.30 g, 63%). LCMS (Method 3): Rt 2.46 min, m/z 364 [MH+].

Aufarbeitung

  1. customThe mixture was degassed
  2. custommicrowave irradiation
  3. temperaturethe reaction mixture heated at 150° C. for a further 2 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 water and brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. customThe residue was purified by FCC

Quellen und Nachweise

ORD-Eintrag
ord-f5b6f790c30f4ddf9b1104b6c9aeffe1
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09440974B2

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