Réaction #45046

Équation de réaction

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

Rendement 10.5%

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

Rendement 10.5%

Solvants

THF

Conditions de réaction

Traitement

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

Mode opératoire

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+)

Source