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Potassium Carbonate → 4-(4-Chloro-2-fluoroanilino)-6-methoxy-7-[2-(2-oxo-1,2-dihydro-1-pyridyl)ethoxy]quinazoline

HRID 1737491
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HRID 1737491 반응식
[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([OH:19])=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:22])[CH:3]=1.Cl[CH2:24][CH2:25][N:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]1=[O:32].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:24][CH2:25][N:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]4=[O:32])=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:22])[CH:3]=1
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참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 127048731-(2-Chloroethyl)pyridin-2(1H)-oneHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

생성물 1

HCID 226250364-(4-Chloro-2-fluoroanilino)-6-methoxy-7-[2-(2-oxo-1,2-dihydro-1-pyridyl)ethoxy]quinazoline수율 12.1%

시약·촉매·용매 2

HCID 962Water용매
HCID 6228
Dimethylformamide
용매

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온도
80 °C

실험 절차

A mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (300 mg, 0.94 mmol), (prepared as described for the starting material in Example 15), 1-(2-chloroethyl)-1,2-dihydro-2-pyridone (175 mg, 1.11 mmol), (J. Am. Chem. Soc. 1951, 73, 3635), and potassium carbonate (260 mg, 1.9 mmol) in DMF (30 ml) was heated at 80° C. for 3 hours, allowed to cool to ambient temperature and stirred for a further 18 hours. The mixture was diluted with water and extracted with ethyl acetate. The extract was washed with water, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol/triethylamine mixtures (100/0/0 increasing to 70/30/0.5) to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-[2-(2-oxo-1,2-dihydro-1-pyridyl)ethoxy]quinazoline (50 mg, 12%).

후처리

  1. custom(prepared
  2. temperatureto cool to ambient temperature
  3. extractionextracted with ethyl acetate
  4. washThe extract was washed with water
  5. dry with materialdried (MgSO4)
  6. customthe solvent removed by evaporation
  7. customThe residue was purified by column chromatography
  8. washeluting with methylene chloride/methanol/triethylamine mixtures (100/0/0 increasing to 70/30/0.5)

출처 및 근거

ORD 기록
ord-a7864add21e34b46897f657a156393e9
출처 데이터셋
uspto-grants-1999_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US05962458

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