Dichloromethane → 2,2-dimethyl-N-(3-methyl-1-(quinolin-5-yl)-1H-pyrazol-5-yl)chroman-6-sulfonamide

HRID 1406557Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1406557
[CH3:1][C:2]1([CH3:16])[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([S:12](Cl)(=[O:14])=[O:13])[CH:8]=2)[O:3]1.[CH3:17][C:18]1[CH:22]=[C:21]([NH2:23])[N:20]([C:24]2[CH:33]=[CH:32][CH:31]=[C:30]3[C:25]=2[CH:26]=[CH:27][CH:28]=[N:29]3)[N:19]=1.ClCCl>N1C=CC=CC=1>[CH3:1][C:2]1([CH3:16])[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([S:12]([NH:23][C:21]3[N:20]([C:24]4[CH:33]=[CH:32][CH:31]=[C:30]5[C:25]=4[CH:26]=[CH:27][CH:28]=[N:29]5)[N:19]=[C:18]([CH3:17])[CH:22]=3)(=[O:14])=[O:13])[CH:8]=2)[O:3]1

Komponenten

5

Edukt 3

HCID 6344DichloromethaneHCID 27797742,2-Dimethyl-6-Chromanesulfonyl ChlorideHCID 866945143-methyl-1-(quinolin-5-yl)-1H-pyrazol-5-amine

Produkt 1

HCID 866945222,2-dimethyl-N-(3-methyl-1-(quinolin-5-yl)-1H-pyrazol-5-yl)chroman-6-sulfonamideAusbeute 10 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1049PyridineLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A stirring mixture of 2,2-dimethylchroman-6-sulfonyl chloride (0.050 g, 0.22 mmol) and 3-methyl-1-(quinolin-5-yl)-1H-pyrazol-5-amine (prepared from Example 4 step b, 0.068 g, 0.26 mmol) in pyridine (1.0 mL) was heated at 80° C. for 15 h. After cooling to room temperature, dichloromethane was added to the reaction mixture and washed with 1 M aqueous saturated bisulfate (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 resulting crude residue was purified by flash chromatography (SiO2, 0-20% ethyl acetate in hexanes), followed 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 9.09 (d, J=4.8 Hz, 1H), 8.38 (d, J=8.4 Hz, 1H), 8.29 (d, J=8.4 Hz, 1H), 7.87 (t, J=7.6 Hz, 1H), 7.66 (dd, J=4.8, 8.8 Hz, 1H), 7.61 (d, J=7.6 Hz, 1H), 7.40-7.38 (m, 2H), 6.72 (d, J=9.2 Hz, 1H), 6.09 (s, 1H), 2.71 (t, J=6.4 Hz, 2H), 2.34 (s, 3H), 1.83 (t, J=6.4 Hz, 2H), 1.36 (s, 6H); MS: (ES) m/z calculated for C24H25N4O3S [M+H]+ 449.2. found 449.1

Aufarbeitung

  1. temperatureAfter cooling to room temperature
  2. washwashed with 1 M aqueous saturated bisulfate (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 resulting crude residue was purified by flash chromatography (SiO2, 0-20% ethyl acetate in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-7323da322a634c1b9dce7e72ef47da4e
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08916601B2

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