Dimethylacetamide → 5-chloro-N-[2-(dimethylamino)ethyl]-N-methyl-6-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)nicotinamide

HRID 81673노트

반응식

HRID 81673 반응식
[Cl:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([CH:16]=1)[C:7]([N:9]([CH2:11][CH2:12][N:13]([CH3:15])[CH3:14])[CH3:10])=[O:8].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:3]([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:4][CH:5]=[C:6]([CH:16]=1)[C:7]([N:9]([CH2:11][CH2:12][N:13]([CH3:15])[CH3:14])[CH3:10])=[O:8]

참가 물질

6

반응물 4

HCID 31374DimethylacetamideHCID 231603824-[(1-Methyl-1H-pyrazol-3-yl)amino]quinazolin-6-olHCID 23665647Potassium tert-butoxideHCID 636929125,6-Dichloro-N-[2-(dimethylamino)ethyl]-N-methylnicotinamide

생성물 1

HCID 426110335-chloro-N-[2-(dimethylamino)ethyl]-N-methyl-6-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)nicotinamide수율 25%

시약·촉매·용매 1

HCID 962Water용매

반응 조건

온도
130 °C

실험 절차

5,6-Dichloro-N-[2-(dimethylamino)ethyl]-N-methylnicotinamide (126 mg, 0.46 mmol) and potassium tert-butoxide (58 mg, 0.52 mmol) were added to an N,N-dimethylacetamide solution (1 ml) of 4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-ol (50 mg, 0.21 mmol), and stirred overnight under a nitrogen atmosphere at 130° C. The reaction solution was cooled with ice, saline water was added, and extracted with chloroform. The organic layer was washed with water, then 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=1:4 to 100:2) to obtain the entitled compound (25 mg, yield: 25%) as a pale yellow solid.

후처리

  1. additionwas added
  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=1:4 to 100:2)

출처 및 근거

ORD 기록
ord-fe47f2e5ab514ed999e3b7fd6c2abc60
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846700B2

반응 노트

불러오는 중…