Reaction #45032

Reaction equation

4-Methoxybenzoyl chloride

tert-butyl 5-amino-3-[(3,5-dimethoxyphenyl)methoxy]pyrazole-1-carboxylate

→

title compound

Yield 20.1%

N-[5-[(3,5-Dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]-4-methoxy-benzamide

Yield 20.1%

Solvents

THF

THF

Conditions

Workup

1. 1
   Temperaturethe solution was heated
2. 2
   Temperatureat reflux for a total of 14 h
3. 3
   OtherThe solvent was evaporated
4. 4
   Otherthe residue was purified by prep
5. 5
   OtherThe product fractions were evaporated to dryness
6. 6
   workup.ADDITION4M HCl in dioxane (1 ml) was added
7. 7
   workup.STIRRINGthe mixture stirred at room temperature for 1 h
8. 8
   Otherevaporated to dryness
9. 9
   OtherThe residue was partitioned between ethyl acetate (6 ml) and aqueous NaHCO3 (6 ml)
10. 10
    Otherthe layers were separated
11. 11
    Extractionthe aqueous layer was re-extracted with ethyl acetate (3×6 ml)
12. 12
    DryingThe combined organic extracts were dried over Na2SO4
13. 13
    Filtrationfiltered
14. 14
    Otherevaporated

Procedure

4-Methoxybenzoyl chloride (54 mg, 0.315 mmol, 1.1 eq) in THF (2 ml) was added dropwise to a solution of tert-butyl 5-amino-3-[(3,5-dimethoxyphenyl)methoxy]pyrazole-1-carboxylate (100 mg, 0.286 mmol, 1 eq) in THF (3 ml) under nitrogen and the solution was heated at reflux for a total of 14 h, then stirred at room temperature for 16 h. The solvent was evaporated and the residue was purified by prep. HPLC, using a gradient of 55-75% MeCN in H2O (containing 1% ammonium hydroxide). The product fractions were evaporated to dryness and taken up in DCM (4 ml). 4M HCl in dioxane (1 ml) was added and the mixture stirred at room temperature for 1 h, then evaporated to dryness. The residue was partitioned between ethyl acetate (6 ml) and aqueous NaHCO3 (6 ml), the layers were separated and the aqueous layer was re-extracted with ethyl acetate (3×6 ml). The combined organic extracts were dried over Na2SO4, filtered and evaporated to afford the title compound as an off-white solid (22 mg, 20% yield); 1H NMR (400.132 MHz, DMSO) δ 3.74 (s, 6H), 3.82 (s, 3H), 5.06 (s, 2H), 5.59 (s, 1H), 6.43 (t, 1H), 6.59 (d, 2H), 7.00 (d, 2H), 7.96 (d, 2H) MS: m/z 384 (MH+)

Source