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

HRID 1517312노트

반응식

HRID 1517312 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

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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-9b2f22b5bb32437b94eed56564e65e3c
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08232284B2

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