Potassium Carbonate → URAT1 inhibitor 7

HRID 2178107노트

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HRID 2178107 반응식
[C:1]([C:3]1[CH:4]=[C:5]([S:10]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][N:15]=2)(=[O:12])=[O:11])[CH:6]=[CH:7][C:8]=1F)#[N:2].[Cl:21][C:22]1[CH:29]=[C:28]([OH:30])[CH:27]=[CH:26][C:23]=1[C:24]#[N:25].C(=O)([O-])[O-].[K+].[K+].C(=O)([O-])O.[Na+]>CS(C)=O.C(OCC)(=O)C>[Cl:21][C:22]1[CH:29]=[C:28]([CH:27]=[CH:26][C:23]=1[C:24]#[N:25])[O:30][C:8]1[CH:7]=[CH:6][C:5]([S:10]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][N:15]=2)(=[O:12])=[O:11])=[CH:4][C:3]=1[C:1]#[N:2]

참가 물질

7

반응물 4

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 5927972-Chloro-4-hydroxybenzonitrileHCID 594366003-cyano-4-fluoro-N-(5-fluoropyridin-2-yl)benzenesulfonamide

생성물 1

HCID 86294663URAT1 inhibitor 7수율 46%

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 8857Ethyl Acetate용매

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온도
80 °C

실험 절차

3-Cyano-4-fluoro-N-(5-fluoropyridin-2-yl)benzenesulfonamide (Preparation 2, 10.5 g, 35.6 mmol) was added to a solution of 2-chloro-4-hydroxybenzonitrile (8.19 g, 53.3 mmol) and potassium carbonate (14.74 g, 106.7 mmol) in dimethylsulfoxide (100 mL) at room temperature. The resulting mixture was stirred at 80° C. for 44 hours. On cooling, the reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution (200 mL) and ethyl acetate (1000 mL) was added. The aqueous layer was separated and the organic layer was washed with saturated aqueous sodium hydrogen carbonate solution (3×200 mL), water (2×200 mL) and brine (2×200 mL). The organic layer was dried over sodium sulphate, filtered and concentrated in vacuo. The residue was purified by reverse phase column chromatography eluting with acetonitrile (containing 0.1% HCO2H): water (containing 0.1% HCO2H) from 0 to 100% to afford the title compound as a white solid (6.982 g, 46%).

후처리

  1. temperatureOn cooling
  2. additionwas added
  3. customThe aqueous layer was separated
  4. washthe organic layer was washed with saturated aqueous sodium hydrogen carbonate solution (3×200 mL), water (2×200 mL) and brine (2×200 mL)
  5. dry with materialThe organic layer was dried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by reverse phase column chromatography
  9. washeluting with acetonitrile (containing 0.1% HCO2H)

출처 및 근거

ORD 기록
ord-be6b74a1d1394616becd589715437aba
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09067922B2

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