Methyl iodide → 3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-1-(3-(methoxymethyl)benzyl)-5,5-dimethylimidazolidine-2,4-dione

HRID 1770629노트

반응식

HRID 1770629 반응식
[CH3:1][C:2]1[C:6]([CH2:7][N:8]2[CH:12]=[C:11]([N:13]3[C:17](=[O:18])[C:16]([CH3:20])([CH3:19])[N:15]([CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][OH:29])[CH:23]=4)[C:14]3=[O:30])[CH:10]=[N:9]2)=[C:5]([CH3:31])[O:4][N:3]=1.[H-].[Na+].I[CH3:35]>CN(C)C=O.C(OCC)(=O)C>[CH3:1][C:2]1[C:6]([CH2:7][N:8]2[CH:12]=[C:11]([N:13]3[C:17](=[O:18])[C:16]([CH3:20])([CH3:19])[N:15]([CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][O:29][CH3:35])[CH:23]=4)[C:14]3=[O:30])[CH:10]=[N:9]2)=[C:5]([CH3:31])[O:4][N:3]=1

참가 물질

6

반응물 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 533739613-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-1-(3-(hydroxymethyl)benzyl)-5,5-dimethylimidazolidine-2,4-dione

생성물 1

HCID 533737453-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-1-(3-(methoxymethyl)benzyl)-5,5-dimethylimidazolidine-2,4-dione수율 36%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-1-(3-(hydroxymethyl)benzyl)-5,5-dimethylimidazolidine-2,4-dione (Example 12-34) (559 mg, 1.32 mmol) in anhydrous dimethylformamide (10 mL) at 0° C., was added sodium hydride (53 mg, 1.32 mmol), followed by iodomethane (99 ul, 1.58 mmol). The reaction was allowed to warm to room temperature and stirred for about 4 hours. The resulting mixture was diluted with ethyl acetate (40 mL) and ice water (10 mL), The organic phase was collected, dried over anhydrous MgSO4, filtered and then concentrated on the rotovap. The residue was purified by reverse phase HPLC (gradient 10% to 100% methanol/water) and further purified by column chromatography (60% EtOAc in hexane). Yield 36%, colorless gel. 1H NMR (DMSO-d6, 400 MHz): δ1.29 (s, 6H), 2.14 (s, 3H), 2.40 (s, 3H), 3.25 (s, 3H), 4.37 (s, 2H), 4.55 (s, 2H), 5.18 (s, 2H), 7.19 (t, 1H) 7.30 (d, 2H), 7.32 (s, 1H), 7.82 (s, 1H) 8.20 (s, 1H). MS 438 (MH+). The title compound was shown to inhibit hT2R08 bitter receptor and had an IC50 of 0.13 μM.

후처리

  1. customThe organic phase was collected
  2. dry with materialdried over anhydrous MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated on the rotovap
  5. customThe residue was purified by reverse phase HPLC (gradient 10% to 100% methanol/water)
  6. customfurther purified by column chromatography (60% EtOAc in hexane)

출처 및 근거

ORD 기록
ord-5738c162851847b8bdc8e3280d669bb0
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09247759B2

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