Hydrochloric Acid → HCID 71731972, Verbindung

HRID 1406569Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1406569
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11](Cl)(=[O:13])=[O:12])=[CH:7][C:6]=1[F:15])([CH3:4])([CH3:3])[CH3:2].[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.[OH-].[Li+].[OH-].[Na+].Cl>CN(C1C=CN=CC=1)C.N1C=CC=CC=1>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:22][C:20]2[N:19]([C:23]3[CH:32]=[CH:31][CH:30]=[C:29]4[C:24]=3[CH:25]=[CH:26][CH:27]=[N:28]4)[N:18]=[C:17]([CH3:16])[CH:21]=2)(=[O:13])=[O:12])=[CH:7][C:6]=1[F:15])([CH3:4])([CH3:3])[CH3:2]

Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 14798Sodium HydroxideHCID 848039791452184-05-2HCID 866945143-methyl-1-(quinolin-5-yl)-1H-pyrazol-5-amine

Produkt 1

HCID 71731972HCID 71731972, VerbindungAusbeute 6,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 1049PyridineLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

A mixture of 4-t-butyl-3-fluorobenzene-1-sulfonyl chloride (0.075 g, 0.30 mmol), 3-methyl-1-(quinolin-5-yl)-1H-pyrazol-5-amine (prepared from Example 4 step b, 0.050 g, 0.22 mmol), and DMAP (0.027 g, 0.22 mmol) in pyridine (1 mL) was heated at 85° C. for 2.5 h with stirring. After cooling to room temperature, 1 M aqueous lithium hydroxide (1 mL) and 1 M aqueous sodium hydroxide (1 mL) were added to the reaction mixture. The resulting mixture was stirred at room temperature for 15 h and neutralized with 1 N aqueous hydrochloric acid. The aqueous layer was extracted with ethyl acetate and the organic layer was washed with aqueous saturated sodium bicarbonate, dried (Na2SO4), filtered, and concentrated in vacuo. The resulting 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, 0.014 mmol, 6%). 1H NMR (400 MHz, CD3OD) δ 8.83 (dd, J=1.6, 4.4 Hz, 1H), 8.08 (dd, J=1.2, 8.4 Hz, 1H), 7.79 (dd, J=7.2, 8.4 Hz, 1H), 7.69 (ddd, J=0.8, 1.6, 7.6 Hz, 1H), 7.44 (dd, J=1.2, 7.2 Hz, 1H), 7.40-7.31 (m, 3H), 7.20 (dd, J=1.6, 7.2 Hz, 1H), 5.88 (s, 1H), 2.21 (s, 3H), 1.39 (s, 9H); MS: (ES) m/z calculated for C23H24FN4O2S [M+H]+ 439.2. found 439.2.

Aufarbeitung

  1. temperatureAfter cooling to room temperature
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. washthe organic layer was washed with aqueous saturated sodium bicarbonate
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting crude residue was purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent)

Quellen und Nachweise

ORD-Eintrag
ord-ec59aec9e72540e9a13d19ff955a05f3
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08916601B2

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