Potassium Carbonate → (5R)-3-{6-[(3,3-dimethyl-1,3-dihydro-2-benzofuran-4-yl)oxy]-3-pyridinyl}-5-ethyl-5-methyl-2,4-imidazolidinedione

HRID 527717노트

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HRID 527717 반응식
[CH3:1][C:2]1([CH3:12])[C:6]2[C:7]([OH:11])=[CH:8][CH:9]=[CH:10][C:5]=2[CH2:4][O:3]1.Cl[C:14]1[N:19]=[CH:18][C:17]([N:20]2[C:24](=[O:25])[C@:23]([CH2:27][CH3:28])([CH3:26])[NH:22][C:21]2=[O:29])=[CH:16][CH:15]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O.C(OCC)(=O)C>[CH3:1][C:2]1([CH3:12])[C:6]2[C:7]([O:11][C:14]3[N:19]=[CH:18][C:17]([N:20]4[C:24](=[O:25])[C@:23]([CH2:27][CH3:28])([CH3:26])[NH:22][C:21]4=[O:29])=[CH:16][CH:15]=3)=[CH:8][CH:9]=[CH:10][C:5]=2[CH2:4][O:3]1

참가 물질

7

반응물 3

HCID 11430Potassium CarbonateHCID 685333883,3-dimethyl-1H-isobenzofuran-4-ol2회HCID 86698458(5R)-3-(6-chloro-3-pyridinyl)-5-ethyl-5-methyl-2,4-imidazolidinedione2회

생성물 1

HCID 57411186(5R)-3-{6-[(3,3-dimethyl-1,3-dihydro-2-benzofuran-4-yl)oxy]-3-pyridinyl}-5-ethyl-5-methyl-2,4-imidazolidinedione수율 45.9%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

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온도
130 °C

실험 절차

3,3-Dimethyl-1,3-dihydro-2-benzofuran-4-ol (Intermediate 193, 68 mg, 0.4 mmol) and (5R)-3-(6-chloropyridin-3-yl)-5-ethyl-5-methylimidazolidine-2,4-dione (Intermediate 194, 126 mg, 0.48 mmol) were dissolved in DMF (1.0 mL) and K2CO3 (143 mg, 1.03 mmol) was added. The resulting suspension was heated to 130° C. under microwave irradiation for 40 minutes. The reaction mixture was diluted with water (25 mL) and ethyl acetate (25 mL), and then two phases were separated. The organic layer was washed with water and brine, dried over Na2SO4 and concentrated under vacuum. The residue was purified by flash chromatography (Biotage system) on silica gel using cyclohexane/ethyl acetate 50:50 as eluent affording the title compound (70 mg) as a white solid.

후처리

  1. customtwo phases were separated
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified by flash chromatography (Biotage system) on silica gel

출처 및 근거

ORD 기록
ord-1dc3d327d3c445d58faaf63d3440e725
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346790B2

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