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

HRID 16754

반응식

HRID 16754 반응식
[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7](Cl)=[O:8])=[CH:5][CH:4]=1.[NH2:12][C:13]1[N:17](C(OC(C)(C)C)=O)[N:16]=[C:15]([O:25][CH2:26][C:27]2[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[C:29]([O:35][CH3:36])[CH:28]=2)[CH:14]=1>C1COCC1>[CH3:34][O:33][C:31]1[CH:32]=[C:27]([CH2:26][O:25][C:15]2[CH:14]=[C:13]([NH:12][C:7](=[O:8])[C:6]3[CH:10]=[CH:11][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[NH:17][N:16]=2)[CH:28]=[C:29]([O:35][CH3:36])[CH:30]=1

참가 물질

4

반응물 2

HCID 7477p-Anisoyl chlorideHCID 66589741Tert-butyl 5-amino-3-[(3,5-dimethoxyphenyl)methoxy]pyrazole-1-carboxylate

생성물 1

HCID 66589902N-[5-[(3,5-Dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]-4-methoxy-benzamide수율 20.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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+)

후처리

  1. temperaturethe solution was heated
  2. temperatureat reflux for a total of 14 h
  3. customThe solvent was evaporated
  4. customthe residue was purified by prep
  5. customThe product fractions were evaporated to dryness
  6. addition4M HCl in dioxane (1 ml) was added
  7. stirringthe mixture stirred at room temperature for 1 h
  8. customevaporated to dryness
  9. customThe residue was partitioned between ethyl acetate (6 ml) and aqueous NaHCO3 (6 ml)
  10. customthe layers were separated
  11. extractionthe aqueous layer was re-extracted with ethyl acetate (3×6 ml)
  12. dry with materialThe combined organic extracts were dried over Na2SO4
  13. filtrationfiltered
  14. customevaporated

출처 및 근거

ORD 기록
ord-8c1cabe2a66a4121aaba72ee67c9dc09
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07737149B2

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