Dichloromethane → 4-t-butyl-N-(1-(quinolin-5-yl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)benzenesulfonamide

HRID 1406564Notes

Reaction equation

HRID 1406564 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11](Cl)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[N:15]1[C:24]2[C:19](=[C:20]([N:25]3[C:29]([NH2:30])=[CH:28][C:27]([C:31]([F:34])([F:33])[F:32])=[N:26]3)[CH:21]=[CH:22][CH:23]=2)[CH:18]=[CH:17][CH:16]=1.ClCCl.[OH-].[Na+]>N1C=CC=CC=1>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:30][C:29]2[N:25]([C:20]3[CH:21]=[CH:22][CH:23]=[C:24]4[C:19]=3[CH:18]=[CH:17][CH:16]=[N:15]4)[N:26]=[C:27]([C:31]([F:34])([F:33])[F:32])[CH:28]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 1398824-t-Butylbenzenesulfonyl chlorideHCID 86694535HCID 86694535, compound

Product 1

HCID 866945344-t-butyl-N-(1-(quinolin-5-yl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)benzenesulfonamideYield 32.5%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 4-t-butylbenzenesulfonyl chloride (0.067 g, 0.29 mmol) and 1-(quinolin-5-yl)-3-(trifluoromethyl)-1H-pyrazol-5-amine (0.011 g, 0.04 mmol) in pyridine (0.5 mL) was heated at 80° C. for 2 h with stirring. After cooling to room temperature, dichloromethane was added to the reaction mixture and washed with 1 M aqueous sodium hydrogen sulfate (1 mL). The aqueous layer was further extracted with dichloromethane (2×5 mL), and the combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude residue was dissolved in methanol (3 mL) and 1 M aqueous sodium hydroxide (1.0 mL, 1.0 mmol), and stirred at room temperature for 1 h. The reaction mixture was concentrated in vacuo and partitioned between dichloromethane (3 mL) and 1 M aqueous sodium hydrogen sulfate (3 mL). The phases were separated and the aqueous layer was further extracted with dichloromethane (2×5 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude residue was purified by reverse phase HPLC(C18 column, acetonitrile-H2O with 0.1% TFA as eluent) to give the title compound as a white solid (0.006 g, 0.013 mmol, 32%). 1H NMR (400 MHz, CDCl3) δ 8.78 (dd, J=1.6, 4.4 Hz, 1H), 8.07 (d, J=8.4 Hz, 1H), 7.66 (s, 1H), 7.63 (s, 1H), 7.55 (t, J=8.4 Hz, 1H), 7.45 (s, 1H), 7.48 (s, 1H), 7.43 (d, J=6.0 Hz, 1H), 7.27-7.24 (m, 1H), 7.09 (d, J=6.0 Hz, 1H), 6.70 (s, 1H), 1.38 (s, 9H); MS: (ES) m/z calculated for C23H22F3N4O2S [M+H]+ 475.2. found 475.3.

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with 1 M aqueous sodium hydrogen sulfate (1 mL)
  3. extractionThe aqueous layer was further extracted with dichloromethane (2×5 mL)
  4. dry with materialthe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe crude residue was dissolved in methanol (3 mL)
  8. concentrationThe reaction mixture was concentrated in vacuo
  9. custompartitioned between dichloromethane (3 mL) and 1 M aqueous sodium hydrogen sulfate (3 mL)
  10. customThe phases were separated
  11. extractionthe aqueous layer was further extracted with dichloromethane (2×5 mL)
  12. dry with materialThe combined organic layers were dried (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customThe crude residue was purified by reverse phase HPLC(C18 column, acetonitrile-H2O with 0.1% TFA as eluent)

Sources & evidence

ORD record
ord-6ea986966a6244ac8d1bbf8275321a4a
Source dataset
uspto-grants-2014_12
Patent number
US08916601B2

Reaction notes

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