Cesium carbonate → 5-(3-(1H-Pyrazol-5-yl)phenyl)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide

HRID 1025100Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1025100
C(=O)([O-])[O-].[Cs+].[Cs+].FC(F)(F)S(O[C:13]1[CH:14]=[CH:15][C:16]2[O:20][C:19]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[C:18]([C:28](=[O:31])[NH:29][CH3:30])[C:17]=2[CH:32]=1)(=O)=O.CC1(C)C(C)(C)OB([C:43]2[CH:44]=[C:45]([C:49]3[NH:53][N:52]=[CH:51][CH:50]=3)[CH:46]=[CH:47][CH:48]=2)O1.O1CCOCC1>CCOC(C)=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.O>[NH:53]1[C:49]([C:45]2[CH:44]=[C:43]([C:13]3[CH:14]=[CH:15][C:16]4[O:20][C:19]([C:21]5[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=5)=[C:18]([C:28]([NH:29][CH3:30])=[O:31])[C:17]=4[CH:32]=3)[CH:48]=[CH:47][CH:46]=2)=[CH:50][CH:51]=[N:52]1

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 59275663(4-Fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl trifluoromethanesulfonateHCID 672115605-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrazole

Produkt 1

HCID 592752185-(3-(1H-Pyrazol-5-yl)phenyl)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamideAusbeute 94,8 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

Cesium carbonate (234 mg, 0.719 mmol) was added to Pd(Ph3P)4 (20.77 mg, 0.018 mmol), 2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl trifluoromethanesulfonate (150 mg, 0.359 mmol), 5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrazole (146 mg, 0.539 mmol). Dioxane (3 mL) and water (599 μL) was added at rt. The reaction was heated to 90° C. overnight. The mixture was diluted with EtOAc and washed with sat NaHCO3, and sat NaCl. The organic phase was dried over Na2SO4, filtered and concentrated and purified by trituration with Et2O to give the titled compound (140 mg, 92%). 1H NMR (400 MHz, DMSO-d6) d ppm 13.40 (1 H, br. s.), 12.91 (1 H, br. s.), 8.45-8.55 (1 H, m), 8.13 (1 H, s), 7.97-8.08 (2 H, m), 7.85-7.95 (1 H, m), 7.73-7.85 (4 H, m), 7.59-7.67 (1 H, m), 7.49-7.58 (1 H, m), 7.35-7.45 (2 H, m), 6.84 (1 H, br. s.), 2.87 (3 H, d, J=4.52 Hz). LC-MS retention time: 1.41 min; m/z (MH+): 412. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters XBridge 5 u 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 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 5% acetonitrile/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% acetonitrile/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode. Additional HPLC method: Solvent A=5% CH3CN/95% H2O/0.1% TFA, Solvent B=95% CH3CN/5% H2O/0.1% TFA, Start % B=10, Final % B=100, Gradient time=15 min, Stop time=18 min, Flow Rate=1 ml/min. Column: Waters Sunfire C-18, 4.6×150 mm, 3.5 mm, Rt=11.86 min, purity=97%; Column: Waters Xbridge Phenyl column 4 6×150 mm, 3.5 mm, Rt=10.97 min, purity=99%.

Aufarbeitung

  1. washwashed
  2. dry with materialThe organic phase was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custompurified by trituration with Et2O

Quellen und Nachweise

ORD-Eintrag
ord-abc8cc283fdb4cae82a2325c3be69b91
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08722688B2

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