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Water → 2-(2,6-Dimethylpyridin-4-yl)-7-(2-isopropoxyethoxy)-5-methoxyquinazolin-4(3H)-one

HRID 591828
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HRID 591828 반응식
[H-].[Na+].[CH:3]([O:6][CH2:7][CH2:8][OH:9])([CH3:5])[CH3:4].[CH3:10][C:11]1[CH:16]=[C:15]([C:17]2[NH:26][C:25](=[O:27])[C:24]3[C:19](=[CH:20][C:21](F)=[CH:22][C:23]=3[O:28][CH3:29])[N:18]=2)[CH:14]=[C:13]([CH3:31])[N:12]=1.O>CS(C)=O>[CH3:10][C:11]1[CH:16]=[C:15]([C:17]2[NH:26][C:25](=[O:27])[C:24]3[C:19](=[CH:20][C:21]([O:9][CH2:8][CH2:7][O:6][CH:3]([CH3:5])[CH3:4])=[CH:22][C:23]=3[O:28][CH3:29])[N:18]=2)[CH:14]=[C:13]([CH3:31])[N:12]=1
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참가 물질

6

반응물 4

HCID 962WaterHCID 7996IsopropylethanediolHCID 24758Sodium hydrideHCID 1363480402-(2,6-dimethyl-pyridin-4-yl)-7-fluoro-5-methoxy-3H-quinazolin-4-one

생성물 1

HCID 1359390732-(2,6-Dimethylpyridin-4-yl)-7-(2-isopropoxyethoxy)-5-methoxyquinazolin-4(3H)-one

시약·촉매·용매 1

HCID 679
Dimethyl Sulfoxide
용매

실험 절차

To a suspension of sodium hydride (60% suspension in mineral oil, 0.24 g, 6.00 mmol) in anhydrous DMSO (10 mL) was added 2-isopropoxy-ethanol at room temperature under nitrogen. The mixture was stirred for 20 minutes at room temperature, then 2-(2,6-dimethyl-pyridin-4-yl)-7-fluoro-5-methoxy-3H-quinazolin-4-one (0.30 g, 1.00 mmol) was added and the reaction mixture was stirred at 80° C. for 16 hours, then cooled to room temperature. Water (50 mL) was added, and the mixture was extracted with a mixture of ethyl acetate and THF (4:1, 200 mL). The organic phase was washed with brine and dried over anhydrous sodium sulfate. Solvent was evaporated, and the crude compound was purified by the Simpliflash system (3:15:82 methanol, ethyl acetate and dichloromethane as eluent) to give the title compound as a white solid. Yield: 127 mg (33%). MP 188-189° C. 1H NMR (400 MHz, CDCl3): δ 11.14 (br s, 1H), 7.72 (s, 2H), 6.86 (d, J=2.34 Hz, 1H), 6.59 (d, J=2.34 Hz, 1H), 4.35-4.15 (m, 2H), 3.97 (s, 3H), 3.89-3.79 (m, 2H), 3.78-3.64 (m, 1H), 2.66 (s, 6H), 1.23 (d, J=5.85 Hz, 6H). MS (ES+) m/z: 384.20 (100%).

후처리

  1. stirringthe reaction mixture was stirred at 80° C. for 16 hours
  2. temperaturecooled to room temperature
  3. extractionthe mixture was extracted with a mixture of ethyl acetate and THF (4:1, 200 mL)
  4. washThe organic phase was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customSolvent was evaporated
  7. customthe crude compound was purified by the Simpliflash system (3:15:82 methanol, ethyl acetate and dichloromethane as eluent)

출처 및 근거

ORD 기록
ord-f6a9210b7945489aa66d15258aa55ab9
출처 데이터셋
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09238640B2

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