Dimethyl Sulfoxide → HCID 117737023, compound

HRID 1504524Notes

Reaction equation

HRID 1504524 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:11]2[C:20]3[C:15](=[CH:16][C:17]([S:21]([O:24]C4C(F)=C(F)C(F)=C(F)C=4F)(=O)=[O:22])=[CH:18][CH:19]=3)[CH:14]=[CH:13][C:12]2=[O:36])[C:5]([O:9][CH3:10])=[N:6][C:7]=1[Cl:8].[N:37]1[CH:42]=[CH:41][CH:40]=[C:39]([NH2:43])[N:38]=1.CS(C)=O.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1.Cl.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([N:11]2[C:20]3[C:15](=[CH:16][C:17]([S:21]([NH:43][C:39]4[N:38]=[N:37][CH:42]=[CH:41][CH:40]=4)(=[O:22])=[O:24])=[CH:18][CH:19]=3)[CH:14]=[CH:13][C:12]2=[O:36])[C:5]([O:9][CH3:10])=[N:6][C:7]=1[Cl:8]

Participants

8

Reactant 4

HCID 679Dimethyl SulfoxideHCID 230373AminopyridazineHCID 2733832Lithium HexamethyldisilazideHCID 117736991HCID 117736991, compound

Product 1

HCID 117737023HCID 117737023, compoundYield 43.6%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A RBF was charged with perfluorophenyl 1-(5,6-dichloro-2-methoxypyridin-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonate (0.68 g, 1.199 mmol) and pyridazin-3-amine (0.137 g, 1.438 mmol). DMSO (2.2 ml) was added to give a solution which was then diluted with THF (7.14 ml). The flask was cooled in an ice-water bath for 15 min, then lithium bis(trimethylsilyl)amide (1M in THF) (2.64 ml, 2.64 mmol) was added dropwise, slowly over 2 min. After 15 min, the mixture was diluted with 1N aq. HCl and EtOAc. The layers were separated, and the aq. layer was extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (100-g SNAP Ultra column, 10-70% of a 3:1 EtOAc/EtOH solution in heptane with 10% DCM as additive). Fractions containing pure product were combined and concentrated to give 1-(5,6-dichloro-2-methoxypyridin-3-yl)-2-oxo-N-(pyridazin-3-yl)-1,2-dihydroquinoline-6-sulfonamide (0.25 g, 0.523 mmol, 43.6% yield) as an off-white solid. m/z (ESI) 478.0 (M+H)+.

Workup

  1. customto give a solution which
  2. temperatureThe flask was cooled in an ice-water bath for 15 min
  3. customThe layers were separated
  4. extractionthe aq. layer was extracted with EtOAc (2×)
  5. dry with materialThe combined organic extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography on silica gel (100-g SNAP Ultra column, 10-70% of a 3:1 EtOAc/EtOH solution in heptane with 10% DCM as additive)
  9. additionFractions containing pure product
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-0584a551c8da4bdfa29aa621c925b204
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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