Reaktion #718090

Reaktionsgleichung

(R,R)-(−)-N,N′-Dimethyl-1,2-cyclohexanediamine

5-iodo-1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-imidazole

Intermediate 119a

5-Iodo-1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-imidazole

5-tert-butyl-2H-pyrazol-3-ylamine

K2CO3

→

title compound

Ausbeute 35.4%

5-tert-Butyl-2-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-imidazol-4-yl}-2H-pyrazol-3-ylamine

Ausbeute 35.4%

Lösungsmittel

water

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigepreviously degassed
2. 2
   SonstigeThe crude reaction mixture
3. 3
   Extraktionextracted with EtOAc (×3)
4. 4
   WaschenThe combined organic layers were washed with brine
5. 5
   Trocknendried (MgSO4)
6. 6
   Einengenconcentrated in vacuo
7. 7
   SonstigeThe resultant residue was purified by FCC on silica
8. 8
   Sonstigeto give a product

Vorschrift

To a mixture of Intermediate 119a (1.50 g, 4.66 mmol), 5-tert-butyl-2H-pyrazol-3-ylamine (648 mg, 4.66 mmol), copper(I)iodide (44 mg, 0.23 mmol) and K2CO3 (1.35 g, 9.78 mmol) was added a solution of toluene (10 mL), previously degassed by using a stream of argon. (R,R)-(−)-N,N′-Dimethyl-1,2-cyclohexanediamine (147 μL, 0.93 mmol) was then added and the reaction mixture was heated at 150° C. for 3 h under microwave irradiation. The crude reaction mixture was poured into water and extracted with EtOAc (×3). The combined organic layers were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by FCC on silica, using a gradient of 0-100% EtOAc in cyclohexane, to give a product consisting of the title compound (550 mg) in mixture with the un-reacted 5-iodo-1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-imidazole isomer. LCMS (Method 4): Rt 2.32 min, m/z 334 [MH+].

Quelle