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

반응식

HRID 1770612 반응식
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

참가 물질

4

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

반응 조건

온도
-78 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-7186b1fea83e4baa90f8c98239fd5cc6
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09247759B2

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