Dimethylacetamide → 3-chloro-N-[2-(dimethylamino)ethyl]-N-methyl-2-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)isonicotinamide

HRID 1517316노트

반응식

HRID 1517316 반응식
[Cl:1][C:2]1[C:16](F)=[N:15][CH:14]=[CH:13][C:3]=1[C:4]([N:6]([CH2:8][CH2:9][N:10]([CH3:12])[CH3:11])[CH3:7])=[O:5].CC(C)([O-])C.[K+].CN(C)C(=O)C.[CH3:30][N:31]1[CH:35]=[CH:34][C:33]([NH:36][C:37]2[C:46]3[C:41](=[CH:42][CH:43]=[C:44]([OH:47])[CH:45]=3)[N:40]=[CH:39][N:38]=2)=[N:32]1>O>[Cl:1][C:2]1[C:16]([O:47][C:44]2[CH:45]=[C:46]3[C:41](=[CH:42][CH:43]=2)[N:40]=[CH:39][N:38]=[C:37]3[NH:36][C:33]2[CH:34]=[CH:35][N:31]([CH3:30])[N:32]=2)=[N:15][CH:14]=[CH:13][C:3]=1[C:4]([N:6]([CH2:8][CH2:9][N:10]([CH3:12])[CH3:11])[CH3:7])=[O:5]

참가 물질

6

반응물 4

HCID 31374DimethylacetamideHCID 231603824-[(1-Methyl-1H-pyrazol-3-yl)amino]quinazolin-6-olHCID 23665647Potassium tert-butoxideHCID 684298433-Chloro-N-[2-(dimethylamino)ethyl]-2-fluoro-N-methylisonicotinamide

생성물 1

HCID 595088873-chloro-N-[2-(dimethylamino)ethyl]-N-methyl-2-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)isonicotinamide수율 84%

시약·촉매·용매 1

HCID 962Water용매

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온도
80 °C

실험 절차

3-Chloro-N-[2-(dimethylamino)ethyl]-2-fluoro-N-methylisonicotinamide (116 mg, 0.45 mmol) and potassium tert-butoxide (70 mg, 0.62 mmol) were added to an N,N-dimethylacetamide solution (1 ml) of 4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-ol (650 mg, 0.25 mmol), and stirred under a nitrogen atmosphere at 80° C. for 2 hours. The reaction solution was cooled to room temperature, water was added, and extracted with chloroform. The organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by amine-type silica gel column chromatography (Biotage NH, hexane:ethyl acetate to chloroform:methanol=1:3 to 100:2) to obtain the entitled compound (101 mg, yield: 84%) as a pale yellow amorphous solid.

후처리

  1. temperatureThe reaction solution was cooled to room temperature
  2. extractionextracted with chloroform
  3. washThe organic layer was washed with water
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by amine-type silica gel column chromatography (Biotage NH, hexane:ethyl acetate to chloroform:methanol=1:3 to 100:2)

출처 및 근거

ORD 기록
ord-8eb94bcbb0314b1493a621f3498c2997
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08232284B2

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