Tetrahydrofuran → 8-(4-chlorophenyl)-7-p-tolyl-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

HRID 2101280Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2101280
Cl[C:2]1[C:3]2[N:4]([C:15](=[O:29])[N:16]([CH2:18][C:19]3[CH:20]=[N:21][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:23][CH:24]=3)[N:17]=2)[CH:5]=[CH:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=1.C1COCC1.[Cl:35][C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=1.C([O-])([O-])=O.[K+].[K+]>CO>[Cl:35][C:36]1[CH:41]=[CH:40][C:39]([C:2]2[C:3]3[N:4]([C:15](=[O:29])[N:16]([CH2:18][C:19]4[CH:20]=[N:21][C:22]([C:25]([F:27])([F:28])[F:26])=[CH:23][CH:24]=4)[N:17]=3)[CH:5]=[CH:6][C:7]=2[C:8]2[CH:9]=[CH:10][C:11]([CH3:14])=[CH:12][CH:13]=2)=[CH:38][CH:37]=1

Komponenten

6

Edukt 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 742994-Chlorophenylboronic acidHCID 577993658-chloro-7-p-tolyl-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

Produkt 1

HCID 160048708-(4-chlorophenyl)-7-p-tolyl-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-oneAusbeute 27,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

To a stirring solution of 8-chloro-7-p-tolyl-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (28 mg, 0.067 mmol) in a 1:1 mixture of THF and methanol (4 mL) at room temperature under argon was added 4-chlorophenylboronic acid (12.5 g, 0.080 mmol), PXPd (11 g, 0.02 mmol), and K2CO3 (18.5 mg, 0.13 mmol). The resulting suspension was heated at 70° C. under argon for 10 min. Analysis by HPLC/MS indicated that starting material had been consumed. After cooling the reaction mixture to room temperature, water (25 mL) and EtOAc (25 mL) were added. The layers were separated. The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified by preparative reverse phase HPLC (without TFA) to obtain 9 mg of the title compound as a white lyophilate. HPLC/MS: retention time=4.16 min, [M+H]+=495. 1H NMR (CDCl3): δ 8.79 (s, 1H), 7.95 (d, J=6.7 Hz, 1H), 7.83 (d, J=6.5 Hz, 1H) 7.69 (d, J=6.7 Hz, 1H), 7.29-7.18 (m, 4H), 7.12 (d, J=6.2 Hz, 2H), 7.00 (d, J=6.2 Hz, 2H), 6.70 (d, J=6.5 Hz, 1H), 5.27 (s, 2H), 2.32 (s, 3H).

Aufarbeitung

  1. customhad been consumed
  2. temperatureAfter cooling the reaction mixture to room temperature
  3. additionwater (25 mL) and EtOAc (25 mL) were added
  4. customThe layers were separated
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by preparative reverse phase HPLC (without TFA)

Quellen und Nachweise

ORD-Eintrag
ord-ed074032b5cc4665b67f83070f6e2ded
Quelldatensatz
uspto-grants-2009_08
Patentnummer
US07572808B2

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