Aminopyridazine → 1-(4-bromo-2-methoxyphenyl)-2-oxo-N-(pyridazin-3-yl)-1,2-dihydroquinoline-6-sulfonamide

HRID 1504435Notes

Reaction equation

HRID 1504435 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18]([O:21]C4C(F)=C(F)C(F)=C(F)C=4F)(=[O:20])=O)=[CH:15][CH:16]=3)[CH:11]=[CH:10][C:9]2=[O:33])=[C:4]([O:34][CH3:35])[CH:3]=1.[N:36]1[CH:41]=[CH:40][CH:39]=[C:38]([NH2:42])[N:37]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18]([NH:42][C:38]4[N:37]=[N:36][CH:41]=[CH:40][CH:39]=4)(=[O:20])=[O:21])=[CH:15][CH:16]=3)[CH:11]=[CH:10][C:9]2=[O:33])=[C:4]([O:34][CH3:35])[CH:3]=1

Participants

5

Reactant 3

HCID 230373AminopyridazineHCID 2733832Lithium HexamethyldisilazideHCID 117737057(S)-Perfluorophenyl 1-(4-bromo-2-methoxyphenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonate

Product 1

HCID 1177372871-(4-bromo-2-methoxyphenyl)-2-oxo-N-(pyridazin-3-yl)-1,2-dihydroquinoline-6-sulfonamideYield 120.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A flask was charged with perfluorophenyl 1-(4-bromo-2-methoxyphenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonate (3.33 g, 5.78 mmol) and pyridazin-3-amine (0.659 g, 6.93 mmol). A septum was attached and THF (28.9 ml) was added. The mixture was cooled to 0° C. and a THF solution of lithium bis(trimethylsilyl)amide (12.13 ml, 12.13 mmol, 1 M) was added dropwise to give a brown solution. The solution was maintained at 0° C. for 20 min. The reaction mixture was partitioned between 1 N HCl (200 mL) and EtOAc (200 mL), the layers were separated and the aqueous layer was extracted with DCM (100 mL) and EtOAc (200 mL). The combined organic layers were dried (Na2SO4) and concentrated to provide 1-(4-bromo-2-methoxyphenyl)-2-oxo-N-(pyridazin-3-yl)-1,2-dihydroquinoline-6-sulfonamide (3.39 g, 6.96 mmol, 120% yield) as a light yellow foam. Although contaminated with solvent, the product was of sufficient purity for use in the next step. m/z (ESI) 485.1 (M−H)−.

Workup

  1. customto give a brown solution
  2. temperatureThe solution was maintained at 0° C. for 20 min
  3. customThe reaction mixture was partitioned between 1 N HCl (200 mL) and EtOAc (200 mL)
  4. customthe layers were separated
  5. extractionthe aqueous layer was extracted with DCM (100 mL) and EtOAc (200 mL)
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-b7dc0800081f49f8b2d5fce6c4463b01
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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