4-Aminophenol → HCID 24757938, compound

HRID 1925271Notes

Reaction equation

HRID 1925271 reaction equation
[ClH:1].[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[N:10]=[CH:9][CH:8]=[C:7]2[O:16][C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][CH:26]=1)[C:23]([C:27](O)=[O:28])=[CH:22][CH:21]=[CH:20]2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC.O[C:62]1[CH:68]=[CH:67][C:65]([NH2:66])=[CH:64][CH:63]=1>CN(C=O)C.CCOC(C)=O>[Cl:1][C:62]1[CH:68]=[CH:67][C:65]([NH:66][C:27]([C:23]2[C:24]3[C:19](=[CH:18][C:17]([O:16][C:7]4[C:6]5[C:11](=[CH:12][C:13]([O:14][CH3:15])=[C:4]([O:3][CH3:2])[CH:5]=5)[N:10]=[CH:9][CH:8]=4)=[CH:26][CH:25]=3)[CH:20]=[CH:21][CH:22]=2)=[O:28])=[CH:64][CH:63]=1

Participants

7

Reactant 4

HCID 4034-AminophenolHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67520189HCID 67520189, compound

Product 1

HCID 24757938HCID 24757938, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A slurry of 6-(6,7-dimethoxy-quinolin-4-yloxy)-naphthalene-1-carboxylic acid hydrochloride (0.200 g, 0.532 mmol, step a), HATU (0.264 g, 0.692 mmol), and Et3N (0.296 ml, 2.12 mmol) in 1.33 mL of DMF under argon was stirred at RT. After 1 h, 4-hydroxyaniline (0.116 g, 1.064 mmol) was added. The solution was stirred at RT for 0.5 h then at 50° C. After 2 h, the reaction was diluted with EtOAc and washed with saturated aqueous NaHCO3, water, and brine. The organic layer was dried (Na2SO4), filtered and concentrated. The residue remaining after concentration was dissolved in acetone and purified by reverse-phase HPLC (pH 1 CH3CN/water solvent system). The fractions containing the desired product were concentrated, dissolved in CH2Cl2, and washed with saturated aqueous NaHCO3 and brine. The organic layer was dried (Na2SO4), filtered and concentrated to afford the titled compound as a pale yellow solid. M+H −467.1. Calc'd for C28H22N2O5−466.49.

Workup

  1. customat 50° C
  2. waitAfter 2 h
  3. washwashed with saturated aqueous NaHCO3, water, and brine
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. concentrationafter concentration
  8. dissolutionwas dissolved in acetone
  9. custompurified by reverse-phase HPLC (pH 1 CH3CN/water solvent system)
  10. additionThe fractions containing the desired product
  11. concentrationwere concentrated
  12. dissolutiondissolved in CH2Cl2
  13. washwashed with saturated aqueous NaHCO3 and brine
  14. dry with materialThe organic layer was dried (Na2SO4)
  15. filtrationfiltered
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-9b7bfaa74e174873ae36cd5c1bd1c6fd
Source dataset
uspto-grants-2012_05
Patent number
US08178557B2

Reaction notes

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