Reaktion #45046

Reaktionsgleichung

NaHMDS

tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazole-1-carboxylate

methyl 2-{[(3-methylisoxazol-5-yl)methyl]amino}-benzoate

→

title compound

Ausbeute 10.5%

N-[5-[2-(3,5-Dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-2-[(3-methyl-1,2-oxazol-5-yl)methylamino]benzamide

Ausbeute 10.5%

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe solution was quenched with satd
2. 2
   workup.ADDITIONaq. NH4Cl, diluted with water (5 ml)
3. 3
   Extraktionextracted with ethyl acetate (3×8 ml)
4. 4
   SonstigeThe crude product was purified by silica column chromatography
5. 5
   Wascheneluting with a gradient of 0-1.5% MeOH in DCM
6. 6
   workup.ADDITIONFractions containing product
7. 7
   Sonstigewere evaporated
8. 8
   Sonstigefurther purified by reverse phase prep
9. 9
   SonstigeHPLC purification
10. 10
    Wascheneluting with a gradient of MeCN/H2O+0.1% TFA

Vorschrift

NaHMDS (1M solution in THF, 0.83 ml, 0.828 mmol, 2.5 eq) was added dropwise to a solution of tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazole-1-carboxylate (90 mg, 0.364 mmol, 1.1 eq) and methyl 2-{[(3-methylisoxazol-5-yl)methyl]amino}-benzoate (115 mg, 0.331 mmol, 1 eq), stirred in THF (4 ml) under nitrogen. The solution was stirred at room temperature for 50 mins. The solution was quenched with satd. aq. NH4Cl, diluted with water (5 ml) and extracted with ethyl acetate (3×8 ml). The crude product was purified by silica column chromatography, eluting with a gradient of 0-1.5% MeOH in DCM. Fractions containing product were evaporated and further purified by reverse phase prep. HPLC purification, eluting with a gradient of MeCN/H2O+0.1% TFA to afford the title compound as an off-white solid (16 mg, 10% yield); 1H NMR (399.902 MHz, DMSO) δ 2.20 (s, 3H), 2.88 (s, 4H), 3.73 (s, 6H), 4.57 (s, 2H), 6.21 (s, 1H), 6.33 (t, 1H), 6.41 (bs, 1H), 6.43 (d, 3H), 6.65 (t, 1H), 6.77 (d, 1H), 7.28-7.34 (m, 1H), 7.75-7.79 (m, 1H), 8.10 (bs, 1H), 10.50 (s, 1H). MS: m/z 462 (MH+)

Quelle