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

HRID 62037

Reaction equation

HRID 62037 reaction equation
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

Participants

8

Reactant 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

Product 1

HCID 904048582-(3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)propyl)isoindoline-1,3-dioneYield 53.3%

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

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]+).

Workup

  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

Sources & evidence

ORD record
ord-5690a4b7280d44d2add56e8ff4e764a1
Source dataset
uspto-grants-2016_09
Patent number
US09445594B2

Linked notes

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