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

HRID 1092025Notes

Reaction equation

HRID 1092025 reaction equation
[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

Participants

4

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

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+)

Workup

  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

Sources & evidence

ORD record
ord-ad84e7cbc0ea44c58c8dc1cc5fd6ee38
Source dataset
uspto-grants-2012_03
Patent number
US08129391B2

Reaction notes

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