Reaktion #45120

Reaktionsgleichung

potassium sodium tartrate

Trimethylaluminium

ethyl 5-(3,3-dimethylpiperazin-1-yl)thiophene-2-carboxylate

5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-amine hydrochloride

→

title compound

Ausbeute 15.5%

N-[5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]-5-(3,3-dimethylpiperazin-1-yl)thiophene-2-carboxamide

Ausbeute 15.5%

Lösungsmittel

water

ethyl acetate

Ethyl acetate

toluene

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   Filtrationthe mixture was filtered through celite
2. 2
   SonstigeThe filtrate was transferred to a separating funnel
3. 3
   Sonstigethe aqueous layer removed
4. 4
   WaschenThe ethyl acetate layer was washed with saturated brine
5. 5
   Trocknendried over magnesium sulphate
6. 6
   FiltrationAfter filtration the solvent
7. 7
   Sonstigewas evaporated
8. 8
   Sonstigeto give the crude product as a yellow gum
9. 9
   SonstigeThe crude product was purified by preparative LCMS
10. 10
    workup.ADDITIONFractions containing the desired compound
11. 11
    Sonstigewere evaporated to dryness

Vorschrift

2M Trimethylaluminium (1.250 ml, 2.50 mmol) in toluene, was added dropwise to a stirred solution of ethyl 5-(3,3-dimethylpiperazin-1-yl)thiophene-2-carboxylate (0.268 g, 1 mmol) and 5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-amine hydrochloride (0.286 g, 1.00 mmol) in toluene (7.14 ml) at 65° C. under nitrogen. The reaction mixture was stirred and heated at 65° C. for 4 h then 50° C. for 18 h followed by 80° C. for 5 h. Ethyl acetate (5 mL) was added to the reaction mixture followed by a solution of potassium sodium tartrate (5 mL, 20% aqueous). More ethyl acetate (50 mL) and water (25 mL) was added and the mixture was filtered through celite. The filtrate was transferred to a separating funnel and the aqueous layer removed. The ethyl acetate layer was washed with saturated brine and then dried over magnesium sulphate. After filtration the solvent was evaporated to give the crude product as a yellow gum. The crude product was purified by preparative LCMS, using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the title compound (0.073 g, 15.48%) as a white solid.

Quelle