Water → 4-[5-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyclopentyl-2-pyrimidinamine

HRID 1062868

Reaktionsgleichung

Reaktionsgleichung von HRID 1062868
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]2[N:8]=[C:9]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:10]([C:11](=O)[C:12]#[C:13]C)=[C:4]2[CH:3]=1.Cl.[CH:24]1([NH:29][C:30]([NH2:32])=[NH:31])[CH2:28][CH2:27][CH2:26][CH2:25]1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]2[N:8]=[C:9]([C:16]3[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=3)[C:10]([C:11]3[CH:12]=[CH:13][N:32]=[C:30]([NH:29][CH:24]4[CH2:28][CH2:27][CH2:26][CH2:25]4)[N:31]=3)=[C:4]2[CH:3]=1

Komponenten

6

Edukt 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 219922331-[5-Chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-butyn-1-oneHCID 178479367HCID 178479367, Verbindung

Produkt 1

HCID 102231334-[5-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyclopentyl-2-pyrimidinamine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution of 1-[5-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-butyn-1-one (0.61 g, 2.0 mmol) in N,N-dimethylformamide was added N-cyclopentyl guanidine hydrochloride (0.67 g, 4.1 mmol) followed by potassium carbonate (0.57 g, 4.1 mmol). The resulting mixture was heated at 80° C. for 12 hours. Upon cooling to room temperature, water was added. The mixture was extracted with ethyl acetate. The ethyl acetate phase was washed with brine, dried (magnesium sulfate), filtered and concentrated in vacuo. The resulting residue was purified by flash chromatography (1:1 ethyl acetate-hexane) to give, after recrystallization from acetonitrile, 4-[5-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyclopentyl-2-pyrimidinamine (0.6 g, 74%) as a white solid. 1H NMR (CDCl3): δ 8.54 (broad s, 1H), 8.40 (d, 1H), 8.04 (d, 1H), 7.60 (q, 2H), 7.16 (t, 2H), 6.88 (dd, 1H), 6.28 (d, 1H), 5.22 (d, 1H), 4.40 (m, 1H), 1.4-2.2 (m, 8H); 19F NMR (CDCl3): δ−112.5; MS m/z 408 (M+1).

Aufarbeitung

  1. temperatureUpon cooling to room temperature
  2. extractionThe mixture was extracted with ethyl acetate
  3. washThe ethyl acetate phase was washed with brine
  4. dry with materialdried (magnesium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by flash chromatography (1:1 ethyl acetate-hexane)
  8. customto give
  9. customafter recrystallization from acetonitrile, 4-[5-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyclopentyl-2-pyrimidinamine (0.6 g, 74%) as a white solid

Quellen und Nachweise

ORD-Eintrag
ord-d87ea8d19162495a85660d6db1a3297a
Quelldatensatz
uspto-grants-2005_11
Patentnummer
US06962914B2

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