Sodium Bicarbonate → 2-(3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)propyl)isoindoline-1,3-dione

HRID 62037

Reaktionsgleichung

Reaktionsgleichung von HRID 62037
Br[C:2]1[N:6]=[CH:5][N:4]([C:7]2[CH:12]=[CH:11][C:10]([O:13][C:14]([F:17])([F:16])[F:15])=[CH:9][CH:8]=2)[N:3]=1.CC1(C)C(C)(C)OB([C:26]2[CH:31]=[CH:30][C:29]([CH2:32][CH2:33][CH2:34][N:35]3[C:43](=[O:44])[C:42]4[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=4)[C:36]3=[O:45])=[CH:28][CH:27]=2)O1.C(=O)(O)[O-].[Na+]>O1CCOCC1.O.C(OCC)(=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:15][C:14]([F:17])([F:16])[O:13][C:10]1[CH:11]=[CH:12][C:7]([N:4]2[CH:5]=[N:6][C:2]([C:26]3[CH:27]=[CH:28][C:29]([CH2:32][CH2:33][CH2:34][N:35]4[C:36](=[O:45])[C:37]5[C:42](=[CH:41][CH:40]=[CH:39][CH:38]=5)[C:43]4=[O:44])=[CH:30][CH:31]=3)=[N:3]2)=[CH:8][CH:9]=1

Komponenten

8

Edukt 3

HCID 516892Sodium BicarbonateHCID 712094283-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazoleHCID 904046722-(3-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propyl)isoindoline-1,3-dione

Produkt 1

HCID 904048582-(3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)propyl)isoindoline-1,3-dioneAusbeute 53,3 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

3-Bromo-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (0.50 g, 1.6 mmol), 2-(3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propyl)isoindoline-1,3-dione (0.64 g, 1.6 mmol), sodium bicarbonate (0.27 g, 3.3 mmol), and tetrakis(triphenylphosphine) palladium(0) (0.19 g, 0.16 mmol) in dioxane (12 mL) and water (4.1 mL) was capped in a 10-20 mL vial and heated on a Biotage Initiator® microwave reactor for 30 minutes at 140° C., with external IR-sensor temperature monitoring from the side of the vessel. The mixture was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography using 0-30% ethyl acetate/B, where B=1:1 dichloromethane/hexanes provided a solid which was dried under house vacuum overnight providing the title compound as a white solid (0.42 g, 53% yield): mp 145-148° C.; 1H NMR (400 MHz, CDCl3) δ 8.54 (d, J=0.8 Hz, 1H), 8.08 (d, J=8.1 Hz, 2H), 7.84 (ddd, J=5.5, 3.0, 0.8 Hz, 2H), 7.82-7.77 (m, 2H), 7.69 (ddd, J=5.5, 3.0, 0.8 Hz, 2H), 7.38 (dt, J=9.0, 1.0 Hz, 2H), 7.31 (d, J=8.0 Hz, 2H), 3.78 (t, J=7.2 Hz, 2H), 2.79-2.71 (m, 2H), 2.08 (p, J=7.5 Hz, 2H); 19F NMR (376 MHz, CDCl3) δ −58.03; ESIMS m/z 493 ([M+H]+).

Aufarbeitung

  1. washwashed with water
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by flash column chromatography
  8. customprovided a solid which
  9. customwas dried under house vacuum overnight

Quellen und Nachweise

ORD-Eintrag
ord-5690a4b7280d44d2add56e8ff4e764a1
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09445594B2

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