2-Methoxyaniline → HCID 86343778, compound

HRID 1504550Notes

Reaction equation

HRID 1504550 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([S:8](=[O:16])(=[O:15])[NH:9][C:10]2[CH:14]=[CH:13][O:12][N:11]=2)=[CH:4][C:3]=1/[CH:17]=[CH:18]/[C:19]([O:21]CC)=O.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH3:74][O:75][C:76]1[CH:82]=[CH:81][CH:80]=[CH:79][C:77]=1[NH2:78]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[O:12]1[CH:13]=[CH:14][C:10]([NH:9][S:8]([C:5]2[CH:4]=[C:3]3[C:2](=[CH:7][CH:6]=2)[N:78]([C:77]2[CH:79]=[CH:80][CH:81]=[CH:82][C:76]=2[O:75][CH3:74])[C:19](=[O:21])[CH:18]=[CH:17]3)(=[O:15])=[O:16])=[N:11]1

Participants

7

Reactant 4

HCID 70002-MethoxyanilineHCID 62657Potassium Phosphate, TribasicHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 117736906HCID 117736906, compound

Product 1

HCID 86343778HCID 86343778, compoundYield 65.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

(E)-Ethyl 3-(2-iodo-5-(N-(isoxazol-3-yl)sulfamoyl)phenyl)acrylate (0.043 g, 0.096 mmol), xantphos (8.33 mg, 0.014 mmol), Pd2(dba)3 (4.39 mg, 4.80 μmol), and freshly ground potassium phosphate (0.061 g, 0.288 mmol) were added to a 1 dram vial and purged with N2. 1,4-dioxane (0.5 ml) and 2-methoxyaniline (0.022 ml, 0.192 mmol) were added and the mixture was evacuated and backfilled with N2 twice and then stirred at 80° C. for 4 hr. The reaction was then cooled to rt and diluted with 1.5 mL MeOH then heated to 80° C. overnight. The reaction was concentrated to remove MeOH, then diluted with EtOAc and 1N HCl. The aqueous layer was extracted twice with EtOAc, the combined organics were washed with brine, dried over Na2SO4, and concentrated. MPLC purification (12 g Snap, 40% [3:1 EtOAc:EtOH]:heptanes) provided N-(isoxazol-3-yl)-1-(2-methoxyphenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (24.8 mg, 0.062 mmol, 65.1% yield) as a light yellow solid. m/z (ESI) 396.0 (M−H)−.

Workup

  1. custompurged with N2
  2. customthe mixture was evacuated
  3. temperatureThe reaction was then cooled to rt
  4. additiondiluted with 1.5 mL MeOH
  5. temperaturethen heated to 80° C. overnight
  6. concentrationThe reaction was concentrated
  7. customto remove MeOH
  8. additiondiluted with EtOAc and 1N HCl
  9. extractionThe aqueous layer was extracted twice with EtOAc
  10. washthe combined organics were washed with brine
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated
  13. customMPLC purification (12 g Snap, 40% [3:1 EtOAc:EtOH]:heptanes)

Sources & evidence

ORD record
ord-0b9952c2bb7f450e94d45fa7a829e4b1
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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