Sodium Carbonate → 3-(3-(Tert-butoxycarbonyl(methyl)carbamoyl)-4-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acid

HRID 44039

Reaktionsgleichung

Reaktionsgleichung von HRID 44039
Cl[C:2]1[CH:7]=[CH:6][N:5]2[N:8]=[C:9]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[C:10]([C:11]([N:13]([CH3:21])[C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:12])=[C:4]2[C:3]=1[F:29].[CH3:30][C:31]1[CH:39]=[CH:38][C:34]([C:35]([OH:37])=[O:36])=[CH:33][C:32]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>O>[C:16]([O:15][C:14]([N:13]([CH3:21])[C:11]([C:10]1[C:9]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)=[N:8][N:5]2[CH:6]=[CH:7][C:2]([C:32]3[CH:33]=[C:34]([CH:38]=[CH:39][C:31]=3[CH3:30])[C:35]([OH:37])=[O:36])=[C:3]([F:29])[C:4]=12)=[O:12])=[O:20])([CH3:19])([CH3:18])[CH3:17]

Komponenten

6

Edukt 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 160860864-Methyl-3-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acidHCID 59233723Tert-butyl 5-chloro-4-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine-3-carbonyl(methyl)carbamate

Produkt 1

HCID 592338363-(3-(Tert-butoxycarbonyl(methyl)carbamoyl)-4-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acid

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

To a degassed solution containing tert-butyl 5-chloro-4-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine-3-carbonyl(methyl)carbamate (0.10 g, 0.24 mmol), 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid (0.078 g, 0.30 mmol), sodium carbonate (0.075 g, 0.71 mmol), dioxane (2.0 mL) and water (0.40 mL) was added tetrakis(tiphenylphosphine)palladium(0) (0.008 g, 0.007 mmol). The mixture was stirred at 95° C. for 18 h. The solution was cooled to room temperature, filtered to remove solids and adjusted to below pH 4 with 1N aqueous hydrochloric acid (2.0 mL). Water was added (10 mL) and the aqueous portion was extracted with ethyl acetate (2×15 mL). The combined organic portions were washed with brine (20 mL) and dried over magnesium sulfate. The mixture was filtered and concentrated to afford 3-(3-(tert-butoxycarbonyl(methyl)carbamoyl)-4-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acid as a residue which was used without further purification. LCMS retention time: 2.467 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Sunfire C18, 5 micron, C18, 4.6×50 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 3 min, a hold time of 1 min, and an analysis time of 4 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 522 (MH+).

Aufarbeitung

  1. temperatureThe solution was cooled to room temperature
  2. filtrationfiltered
  3. customto remove solids
  4. additionWater was added (10 mL)
  5. extractionthe aqueous portion was extracted with ethyl acetate (2×15 mL)
  6. washThe combined organic portions were washed with brine (20 mL)
  7. dry with materialdried over magnesium sulfate
  8. filtrationThe mixture was filtered
  9. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-ba4eb59911b84eb2ba161557a3344da6
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08536338B2

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