Dichloromethane → N-(3-methyl-1-(quinolin-5-yl)-1H-pyrazol-5-yl)-4-(trifluoromethoxy)benzenesulfonamide

HRID 1406548Notes

Reaction equation

HRID 1406548 reaction equation
[F:1][C:2]([F:15])([F:14])[O:3][C:4]1[CH:9]=[CH:8][C:7]([S:10](Cl)(=[O:12])=[O:11])=[CH:6][CH:5]=1.[CH3:16][C:17]1[CH:21]=[C:20]([NH2:22])[N:19]([C:23]2[CH:32]=[CH:31][CH:30]=[C:29]3[C:24]=2[CH:25]=[CH:26][CH:27]=[N:28]3)[N:18]=1.ClCCl>N1C=CC=CC=1>[CH3:16][C:17]1[CH:21]=[C:20]([NH:22][S:10]([C:7]2[CH:8]=[CH:9][C:4]([O:3][C:2]([F:15])([F:14])[F:1])=[CH:5][CH:6]=2)(=[O:12])=[O:11])[N:19]([C:23]2[CH:32]=[CH:31][CH:30]=[C:29]3[C:24]=2[CH:25]=[CH:26][CH:27]=[N:28]3)[N:18]=1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 523102p-(Trifluoromethoxy)benzenesulphonyl chlorideHCID 866945143-methyl-1-(quinolin-5-yl)-1H-pyrazol-5-amine

Product 1

HCID 71731558N-(3-methyl-1-(quinolin-5-yl)-1H-pyrazol-5-yl)-4-(trifluoromethoxy)benzenesulfonamideYield 10%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
80 °C

Procedure

To a stirring mixture of 4-(trifluoromethoxy)benzene-1-sulfonyl chloride (0.060 g, 0.23 mmol) and 3-methyl-1-(quinolin-5-yl)-1H-pyrazol-5-amine (prepared from Example 4 step b, 0.050 g, 0.22 mmol) in pyridine (1.0 mL) was heated at 80° C. for 1 h. 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 purified by flash chromatography (SiO2, 2-10% methanol in dichloromethane) and purification by reverse phase HPLC(C18 column, acetonitrile-H2O with 0.1% TFA as eluent) to give the title compound as a white solid (0.010 g, 0.022 mmol, 10%). 1H NMR (400 MHz, CDCl3) δ 8.75 (d, J=4.0 Hz, 1H), 8.01 (d, J=8.8 Hz, 1H), 7.71 (s, 1H), 7.69 (s, 1H), 7.56 (t, J=8.4 Hz, 1H), 7.49 (d, J=8.4 Hz, 1H), 7.21-7.17 (m, 4H), 6.12 (s, 1H), 2.34 (s, 3H); MS: (ES) m/z calculated for C20H16F3N4O3S [M+H]+ 449.1. found 449.7.

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. customThe crude residue was purified by flash chromatography (SiO2, 2-10% methanol in dichloromethane) and purification by reverse phase HPLC(C18 column, acetonitrile-H2O with 0.1% TFA as eluent)

Sources & evidence

ORD record
ord-37b23fb66b164eea896bcc88f0debac1
Source dataset
uspto-grants-2014_12
Patent number
US08916601B2

Reaction notes

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