Cesium carbonate → 3-(2-(4-Fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)benzoic acid

HRID 44000

Reaktionsgleichung

Reaktionsgleichung von HRID 44000
FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][N:10]2[N:13]=[C:14]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[C:15]([C:16](=[O:19])[NH:17][CH3:18])=[C:9]2[CH:8]=1)(=O)=O.B([C:32]1[CH:33]=[C:34]([CH:38]=[CH:39][CH:40]=1)[C:35]([OH:37])=[O:36])(O)O.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>O>[F:26][C:23]1[CH:22]=[CH:21][C:20]([C:14]2[C:15]([C:16](=[O:19])[NH:17][CH3:18])=[C:9]3[CH:8]=[C:7]([C:32]4[CH:33]=[C:34]([CH:38]=[CH:39][CH:40]=4)[C:35]([OH:37])=[O:36])[CH:12]=[CH:11][N:10]3[N:13]=2)=[CH:25][CH:24]=1

Komponenten

6

Edukt 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 27339573-Carboxyphenylboronic acidHCID 592337772-(4-Fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl trifluoromethanesulfonate

Produkt 1

HCID 592336733-(2-(4-Fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)benzoic acid

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

To a degassed solution containing 2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl trifluoromethanesulfonate (0.19 g, 0.44 mmol), 3-boronobenzoic acid (0.11 g, 0.67 mmol), cesium carbonate (0.22 g, 0.67 mmol), dioxane (3.7 mL) and water (0.74 mL) was added tetrakis(tiphenylphosphine)palladium(0) (0.0090 g, 0.010 mmol). The solution was maintained at 95° C. for 7 h. The solution was cooled to room temperature, concentrated and dissolved in a solution containing water and methanol (1.8/1, 14 mL). The solution was filtered to remove fine particulates and washed with dichloromethane (3×5 mL). The aqueous portion was concentrated to dryness to afford 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)benzoic acid as a pale grey solid which was used without further purification. LCMS: retention time: 1.830 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna, 10u, C18, 3.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 4 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 4 min, a hold time of 1 min, and an analysis time of 5 min where solvent A was 10% CH3CN/90% H2O/10 mM TFA and solvent B was 10% H2O/90% CH3CN/10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 390 (MH+).

Aufarbeitung

  1. temperatureThe solution was cooled to room temperature
  2. concentrationconcentrated
  3. dissolutiondissolved in a solution
  4. additioncontaining water and methanol (1.8/1, 14 mL)
  5. filtrationThe solution was filtered
  6. customto remove fine particulates
  7. washwashed with dichloromethane (3×5 mL)
  8. concentrationThe aqueous portion was concentrated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-86102eda547746f9a5bb8658c1d7adf3
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08536338B2

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