반응 #45032

반응 방정식

4-Methoxybenzoyl chloride

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

→

title compound

수율 20.1%

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

수율 20.1%

용매

THF

THF

반응 조건

후처리

1. 1
   온도the solution was heated
2. 2
   온도at reflux for a total of 14 h
3. 3
   기타The solvent was evaporated
4. 4
   기타the residue was purified by prep
5. 5
   기타The 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
   기타evaporated to dryness
9. 9
   기타The residue was partitioned between ethyl acetate (6 ml) and aqueous NaHCO3 (6 ml)
10. 10
    기타the layers were separated
11. 11
    추출the aqueous layer was re-extracted with ethyl acetate (3×6 ml)
12. 12
    건조The combined organic extracts were dried over Na2SO4
13. 13
    여과filtered
14. 14
    기타evaporated

실험 절차

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+)

출처