N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine → 4-chloro-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)quinoline-7-sulfonamide

HRID 1473516Notes

Reaction equation

HRID 1473516 reaction equation
[CH3:1][O:2][C:3]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:4]=1[CH2:5][NH:6][C:7]1[S:11][N:10]=[CH:9][N:8]=1.[Cl:18][C:19]1[C:28]2[C:23](=[CH:24][C:25]([S:29](OC3C(F)=C(F)C(F)=C(F)C=3F)(=[O:31])=[O:30])=[CH:26][CH:27]=2)[N:22]=[CH:21][CH:20]=1>C1COCC1.[Cl-].[NH4+].O.CCOC(C)=O.CCCCCCC>[Cl:18][C:19]1[C:28]2[C:23](=[CH:24][C:25]([S:29]([N:6]([CH2:5][C:4]3[CH:12]=[CH:13][C:14]([O:16][CH3:17])=[CH:15][C:3]=3[O:2][CH3:1])[C:7]3[S:11][N:10]=[CH:9][N:8]=3)(=[O:30])=[O:31])=[CH:26][CH:27]=2)[N:22]=[CH:21][CH:20]=1

Participants

8

Reactant 2

HCID 57732216N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amineHCID 86687458Perfluorophenyl 4-chloroquinoline-7-sulfonate

Product 1

HCID 866875714-chloro-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)quinoline-7-sulfonamideYield 82%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolventHCID 8900HeptaneSolventHCID 25517Ammonium ChlorideSolvent

Procedure

A flask was charged with N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine (302 mg, 1.204 mmol) and THF (5471 μl) to give a clear solution. The flask was cooled in a dry ice-acetone bath for 5 min, and then a solution of perfluorophenyl 4-chloroquinoline-7-sulfonate (448.3 mg, 1.094 mmol) in THF (1 mL with a 0.5 mL syringe wash) was added drop wise. After 1 h, the mixture was diluted with saturated aq. ammonium chloride, water, and EtOAc, and the layers were separated. The organic layer was dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (40-g Redi-Sep Gold column, 20-70% EtOAc/Heptane) to give an off-white solid. The solid was taken up in heptane and filtered. The collected solid was washed with heptane (2×), then dried under a stream of N2 (g) for 2 h to give 4-chloro-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)quinoline-7-sulfonamide (426 mg, 0.893 mmol, 82% yield) as a white solid. m/z (ESI) 477.0 (M+H)+.

Workup

  1. customto give a clear solution
  2. temperatureThe flask was cooled in a dry ice-acetone bath for 5 min
  3. customthe layers were separated
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography on silica gel (40-g Redi-Sep Gold column, 20-70% EtOAc/Heptane)
  8. customto give an off-white solid
  9. filtrationfiltered
  10. washThe collected solid was washed with heptane (2×)
  11. dry with materialdried under a stream of N2 (g) for 2 h

Sources & evidence

ORD record
ord-fefeabc659fa45ee963eec79e3077c8d
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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