Boron tribromide → 3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-1-(3-hydroxy-5-methoxybenzyl)-5,5-dimethylimidazolidine-2,4-dione

HRID 1770612

Reaktionsgleichung

Reaktionsgleichung von HRID 1770612
C[O:2][C:3]1[CH:4]=[C:5]([CH:29]=[C:30]([O:32][CH3:33])[CH:31]=1)[CH2:6][N:7]1[C:11]([CH3:13])([CH3:12])[C:10](=[O:14])[N:9]([C:15]2[CH:16]=[N:17][N:18]([CH2:20][C:21]3[C:22]([CH3:27])=[N:23][O:24][C:25]=3[CH3:26])[CH:19]=2)[C:8]1=[O:28].B(Br)(Br)Br>ClCCl>[CH3:27][C:22]1[C:21]([CH2:20][N:18]2[CH:19]=[C:15]([N:9]3[C:10](=[O:14])[C:11]([CH3:13])([CH3:12])[N:7]([CH2:6][C:5]4[CH:29]=[C:30]([O:32][CH3:33])[CH:31]=[C:3]([OH:2])[CH:4]=4)[C:8]3=[O:28])[CH:16]=[N:17]2)=[C:25]([CH3:26])[O:24][N:23]=1

Komponenten

4

Edukt 2

HCID 25134Boron tribromideHCID 533751511-(3,5-dimethoxybenzyl)-3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-5,5-dimethylimidazolidine-2,4-dione

Produkt 1

HCID 533736383-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-1-(3-hydroxy-5-methoxybenzyl)-5,5-dimethylimidazolidine-2,4-dioneAusbeute 47 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

1-(3,5-dimethoxybenzyl)-3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-5,5-dimethylimidazolidine-2,4-dione (Example 12-18) (114 mg, 0.252 mmol) was dissolved in dichloromethane (1 mL). The mixture was cooled down to −78° C. and boron tribromide (1.0 M solution in dichloromethane, 1.25 mL) was added dropwise. After complete addition, the mixture was allowed to warm to room temperature and stirring continued for 3 hours. The mixture was quenched with water and the organic phase was separated, dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure. The residue was suspended in methanol (1 mL) and purified by reverse phase HPLC (25 minute gradient: acetonitrile/water). Yield 47% (45 mg), white solid. 1H NMR (DMSO-d6, 400 MHz): . s, 6H), 2.16 (s, 3H), 2.42 (s, 3H), 3.67 (s, 3H), 4.43 (s, 2H), 5.20 (s, 2H), 6.22 (t, J=2.4 Hz, 1H), 6.39 (m, 2H), 7.83 (d, J=0.4 Hz, 1H), 8.21 (s, 1H), 9.40 (br s, 1H). Mp. 72-74° C. MS 440 (MH+). The title compound was shown to inhibit hT2R08 bitter receptor and had an IC50 of 0.02 μM.

Aufarbeitung

  1. additionAfter complete addition
  2. temperatureto warm to room temperature
  3. customThe mixture was quenched with water
  4. customthe organic phase was separated
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. custompurified by reverse phase HPLC (25 minute gradient: acetonitrile/water)

Quellen und Nachweise

ORD-Eintrag
ord-7186b1fea83e4baa90f8c98239fd5cc6
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09247759B2

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