2-Methyl-5-Nitroaniline → N-(5-Amino-2-methyl-phenyl)-4-oxo-1H-quinoline-3-carboxamide

HRID 401435

Reaction equation

HRID 401435 reaction equation
[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[C:12]([OH:14])=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH3:48][C:49]1[CH:54]=[CH:53][C:52]([N+:55]([O-])=O)=[CH:51][C:50]=1[NH2:58].O.O.Cl[Sn]Cl.C([O-])(O)=O.[Na+]>C1COCC1>[NH2:55][C:52]1[CH:53]=[CH:54][C:49]([CH3:48])=[C:50]([NH:58][C:12]([C:3]2[C:2](=[O:1])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[NH:5][CH:4]=2)=[O:14])[CH:51]=1

Participants

8

Reactant 6

HCID 74442-Methyl-5-NitroanilineHCID 61436Stannous chloride dihydrateHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178524710HCID 178524710, compound

Product 1

HCID 57567293N-(5-Amino-2-methyl-phenyl)-4-oxo-1H-quinoline-3-carboxamideYield 8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 4-hydroxy-quinoline-3-carboxylic acid (A-1) (50 mg, 0.26 mmol), HBTU (99 mg, 0.26 mmol) and DIEA (138 μL, 0.79 mmol) in THF (2.6 mL) was added 2-methyl-5-nitro-phenylamine (40 mg, 0.26 mmol). The mixture was heated at 150° C. in the microwave for 20 min and the resulting solution was concentrated. The residue was dissolved in EtOH (2 mL) and SnCl2.2H2O (293 mg, 1.3 mmol) was added. The reaction was stirred at room temperature overnight. The reaction mixture was basified with sat. NaHCO3 solution to pH 7-8 and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was dissolved in DMSO and purified by HPLC (10-99% CH3CN/H2O) to yield the product, N-(5-amino-2-methyl-phenyl)-4-oxo-1H-quinoline-3-carboxamide (94) (6 mg, 8%). HPLC ret. time 2.06 min, 10-99% CH3CN, 5 min run; ESI-MS 294.2 m/z (MH+).

Workup

  1. concentrationthe resulting solution was concentrated
  2. dissolutionThe residue was dissolved in EtOH (2 mL)
  3. extractionextracted with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in DMSO
  9. custompurified by HPLC (10-99% CH3CN/H2O)

Sources & evidence

ORD record
ord-1e99e05502ef45658eed27a4fe0a6d2f
Source dataset
uspto-grants-2014_06
Patent number
US08741925B2

Linked notes

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