Hydrochloric Acid → HCID 71731969, Verbindung

HRID 1406575Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1406575
[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].[F:16][CH2:17][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.[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:23][C:21]2[N:20]([C:24]3[CH:33]=[CH:32][CH:31]=[C:30]4[C:25]=3[CH:26]=[CH:27][CH:28]=[N:29]4)[N:19]=[C:18]([CH2:17][F:16])[CH:22]=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 86694544HCID 86694544, Verbindung

Produkt 1

HCID 71731969HCID 71731969, VerbindungAusbeute 7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 1049PyridineLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

To a mixture of 4-t-butyl-3-fluorobenzene-1-sulfonyl chloride (prepared from Example 27 step c, 0.050 g, 0.20 mmol), 3-(fluoromethyl)-1-(quinolin-5-yl)-1H-pyrazol-5-amine (0.025 g, 0.10 mmol), and DMAP (0.012 g, 0.095 mmol) in pyridine (3 mL) was heated at 85° C. for 2 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 and heated at 75° C. for 1 h. After cooling to room temperature, the reaction mixture was 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 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 (0.003 g, 0.007 mmol, 7%). 1H NMR (400 MHz, CD3OD) 8.83 (dd, J=4.4, 11.6 Hz, 1H), 8.10 (dd, J=1.2, 8.8 Hz, 1H), 7.83 (ddd, J=1.6, 7.6, 8.8 Hz, 1H), 7.63 (dd, J=0.8, 8.8 Hz, 1H), 7.53 (dd, J=0.8, 7.6 Hz, 1H), 7.41 (dd, J=1.6, 8.4 Hz, 1H), 7.38-7.31 (m, 2H), 7.24 (dd, J=1.6, 12.4 Hz, 1H), 6.05 (d, J=1.6 Hz, 1H), 5.28 (s, 1H), 5.16 (s, 1H), 1.40 (d, J=0.8 Hz, 9H); MS: (ES) m/z calculated for C23H26N5O2S [M+H]+ 457.2. found 457.2.

Aufarbeitung

  1. temperatureAfter cooling to room temperature
  2. temperatureheated at 75° C. for 1 h
  3. temperatureAfter cooling to room temperature
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. washthe organic layer was washed with aqueous saturated sodium bicarbonate
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude residue was purified by reverse phase HPLC(C18 column, acetonitrile-H2O with 0.1% TFA as eluent)

Quellen und Nachweise

ORD-Eintrag
ord-65371b0824a7456bae5f35baea2685ca
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08916601B2

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