CasNo： 849217-68-1
MF： C28H24FN3O5
The invention relates to a preparation m...
The invention provides a synthesis metho...
The preparation method is simple, the re...
This invention is directed to the treatm...
4-((6,7-dimethoxyquinolin-4-yl)oxy)aniline
((4-fluorophenyl)carbamoyl)cyclopropanecarboxylic acid
cabozantinib
| Conditions | Yield |
|---|---|
|
With
O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine;
In
N,N-dimethyl-formamide;
at 60 ℃;
Solvent;
Reagent/catalyst;
Temperature;
|
93.1% |
|
With
triethylamine; HATU;
In
dichloromethane;
at 20 - 40 ℃;
for 3h;
Reagent/catalyst;
Large scale;
|
92.3% |
|
With
1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine;
In
dichloromethane; N,N-dimethyl-formamide;
at 20 ℃;
Temperature;
Reagent/catalyst;
Large scale;
|
91% |
|
With
dicyclohexyl-carbodiimide;
In
dichloromethane;
for 10h;
Reflux;
|
86% |
|
With
dicyclohexyl-carbodiimide;
In
dichloromethane;
for 10h;
Reflux;
|
86% |
|
With
N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate;
In
N,N-dimethyl-formamide;
at 20 ℃;
for 20h;
|
42% |
|
((4-fluorophenyl)carbamoyl)cyclopropanecarboxylic acid;
With
N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate;
In
N,N-dimethyl-formamide;
for 0.166667h;
4-((6,7-dimethoxyquinolin-4-yl)oxy)aniline;
In
N,N-dimethyl-formamide;
at 20 ℃;
for 20h;
|
42% |
|
With
1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; ethyl 2-cyanoacetate;
In
N,N-dimethyl-formamide;
at 20 ℃;
|
3.45 g |
|
With
potassium carbonate;
In
tetrahydrofuran; water;
Large scale;
|
4-((6,7-dimethoxyquinolin-4-yl)oxy)aniline
methyl 1-((4-fluorophenyl)amidomethyl)cyclopropyl-1-carboxylate
cabozantinib
| Conditions | Yield |
|---|---|
|
With
sodium hexamethyldisilazane;
In
tetrahydrofuran;
at 0 - 20 ℃;
for 4h;
Reagent/catalyst;
|
94.6% |
|
With
sodium hexamethyldisilazane;
In
tetrahydrofuran;
at -5 - 5 ℃;
|
92.9% |
|
4-((6,7-dimethoxyquinolin-4-yl)oxy)aniline;
With
sodium methylate;
In
toluene;
at 63 - 100 ℃;
methyl 1-((4-fluorophenyl)amidomethyl)cyclopropyl-1-carboxylate;
In
toluene;
|
62% |
|
4-((6,7-dimethoxyquinolin-4-yl)oxy)aniline;
With
sodium methylate;
In
toluene;
at 100 ℃;
for 1h;
Inert atmosphere;
methyl 1-((4-fluorophenyl)amidomethyl)cyclopropyl-1-carboxylate;
In
toluene;
at 110 ℃;
for 4h;
Concentration;
Temperature;
Inert atmosphere;
|
62% |
6,7-dimethoxyquinolin-4-yl trifluoromethanesulfonate
N-(4-fluorophenyl)-N'-(4-hydroxyphenyl)cyclopropane-1,1-dicarboxamide
4-((6,7-dimethoxyquinolin-4-yl)oxy)aniline
4-fluoroaniline
Cabozantinib malate salt
cabozantinib-N-oxide
