Potassium Phosphate, Tribasic → 2-(4-{3-[3-({[(2,2,2-trifluoroethyl)amino]carbonyl}amino)phenyl]imidazo[1,2-b]pyridazin-7-yl}-1H-pyrazol-1-yl)propanoic acid

HRID 407027

Reaktionsgleichung

Reaktionsgleichung von HRID 407027
Cl[C:2]1[CH:7]=[N:6][N:5]2[C:8]([C:11]3[CH:12]=[C:13]([NH:17][C:18]([NH:20][CH2:21][C:22]([F:25])([F:24])[F:23])=[O:19])[CH:14]=[CH:15][CH:16]=3)=[CH:9][N:10]=[C:4]2[CH:3]=1.CC1(C)C(C)(C)OB([C:34]2[CH:35]=[N:36][N:37]([CH:39]([CH3:45])[C:40]([O:42]CC)=[O:41])[CH:38]=2)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:23][C:22]([F:25])([F:24])[CH2:21][NH:20][C:18]([NH:17][C:13]1[CH:12]=[C:11]([C:8]2[N:5]3[N:6]=[CH:7][C:2]([C:34]4[CH:35]=[N:36][N:37]([CH:39]([CH3:45])[C:40]([OH:42])=[O:41])[CH:38]=4)=[CH:3][C:4]3=[N:10][CH:9]=2)[CH:16]=[CH:15][CH:14]=1)=[O:19]

Komponenten

7

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 59492972Ethyl 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propanoateHCID 67980172N-[3-(7-chloroimidazo[1,2-b]pyridazin-3-yl)phenyl]-N'-(2,2,2-trifluoroethyl)urea

Produkt 1

HCID 679802202-(4-{3-[3-({[(2,2,2-trifluoroethyl)amino]carbonyl}amino)phenyl]imidazo[1,2-b]pyridazin-7-yl}-1H-pyrazol-1-yl)propanoic acid

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of N-[3-(7-chloroimidazo[1,2-b]pyridazin-3-yl)phenyl]-N′-(2,2,2-trifluoroethyl)urea (0.206 g, 0.556 mmol, Example 30, Step 3), ethyl 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propanoate (0.18 g, 0.61 mmol), tetrakis(triphenylphosphine)palladium(0) (32.1 mg, 0.00278 mmol) and K3PO4 (0.30 g, 1.4 mmol) in 1,4-dioxane (3.0 mL) and water (2.0 mL) was heated at 100° C. under an atmosphere of nitrogen for 3 h. After cooling, the reaction mixture was adjusted to pH=4, extracted with ethyl acetate (3×30 mL), and washed with brine. The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure to afford the crude product without further purification. LCMS (M+H)+: m/z=474.1.

Aufarbeitung

  1. temperatureAfter cooling
  2. extractionextracted with ethyl acetate (3×30 mL)
  3. washwashed with brine
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-0ca159db230a4bffb45f9bbcdc7ac3b0
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08754114B2

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