Sodium Hydroxide → 2-[3-(4-fluorophenyl)-1-(2-hydroxyethyl)-4-(4-pyridinyl)-1H-pyrazol-5-yl]cyclopropanecarboxylic acid

HRID 1058011Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1058011
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13]3[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=3)=[C:11]([CH:19]3[CH2:21][CH:20]3[C:22]([O:24]CC)=[O:23])[N:10]([CH2:27][CH2:28][OH:29])[N:9]=2)=[CH:4][CH:3]=1.C1CC(NC2C3C(=CC(Cl)=C(Cl)C=3)C(C3C=CN=CC=3)=NN=2)CC1.[OH-].[Na+]>CO.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13]3[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=3)=[C:11]([CH:19]3[CH2:21][CH:20]3[C:22]([OH:24])=[O:23])[N:10]([CH2:27][CH2:28][OH:29])[N:9]=2)=[CH:4][CH:3]=1

Komponenten

6

Edukt 3

HCID 14798Sodium HydroxideHCID 22037272ethyl 2-[3-(4-fluorophenyl)-1-(2-hydroxyethyl)-4-(4-pyridinyl)-1H-pyrazol-5-yl]cyclopropanecarboxylateHCID 1170725486,7-dichloro-N-cyclopentyl-4-(pyridin-4-yl)phthalazin-1-amine

Produkt 1

HCID 220373372-[3-(4-fluorophenyl)-1-(2-hydroxyethyl)-4-(4-pyridinyl)-1H-pyrazol-5-yl]cyclopropanecarboxylic acid

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittel

Versuchsvorschrift

To a solution of ethyl 2-[3-(4-fluorophenyl)-1-(2-hydroxyethyl)-4-(4-pyridinyl)-1H-pyrazol-5-yl]cyclopropanecarboxylate prepared in accordance with Example A-196 (0.21 g, 0.00045 mol) in 10 mL of methanol was added a solution of sodium hydroxide (0.09 g, 0.0022 mol) in 2 mL of water. The reaction mixture was stirred at reflux for 6 hours. After the solvent was removed, the residue was dissolved with 10 mL of 1N HCl and stirred for 30 minutes. The pH was then adjusted to 5-6 by addition of 1N sodium hydroxide solution and then extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium and filtered. The filtrate was concentrated and the crude was purified by recrystallization from ethanol and ether to give 0.1 g of product, 2-[3-(4-fluorophenyl)-1-(2-hydroxyethyl)-4-(4-pyridinyl)-1H-pyrazol-5-yl]cyclopropanecarboxylic acid, as a white solid (60% yield), mp: 253-255° C.; 1H NMR (CD3OD): δ 8.46 (m, 2H), 7.32 (m, 2H), 7.25 (m, 2H), 7.04 (m, 2H), 4.39 (t, J=5.0 Hz, 2H), 4.03 (m, 2H), 2.60 (m, 1H), 1.51 (m, 2H), 0.97 (m, 2H); Anal. Calc'd For C20H18FN3O3: C, 65.39; H, 4.94; N, 11.44. Found: C, 64.92; H, 4.77; N, 11.20.

Aufarbeitung

  1. temperatureat reflux for 6 hours
  2. customAfter the solvent was removed
  3. dissolutionthe residue was dissolved with 10 mL of 1N HCl
  4. stirringstirred for 30 minutes
  5. additionThe pH was then adjusted to 5-6 by addition of 1N sodium hydroxide solution
  6. extractionextracted with ethyl acetate
  7. washThe organic layer was washed with brine
  8. dry with materialdried over magnesium
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated
  11. customthe crude was purified by recrystallization from ethanol and ether

Quellen und Nachweise

ORD-Eintrag
ord-e1393978b4c9472480c6927fc71864d8
Quelldatensatz
uspto-grants-2003_02
Patentnummer
US06514977B1

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