Overview[1][2]
3-Aminobenzamidine dihydrochloride belongs to the amidine organic matter. It can be used as an organic intermediate. 3-nitrobenzamidine hydrochloride can be prepared from trinitrobenzonitrile, and then the nitrobenzene dihydrochloride can be reduced to Preparation of 3-aminobenzamidine dihydrochloride.
Preparation[1-2]
Step 1,
Weigh 74g (0.5mol) of 3-nitrobenzonitrile into a 250mL round-bottomed flask, add 200mL of methanol to dissolve it, and add 5.6g (0.052mol) of a methanol solution of sodium methoxide with a mass percentage of 50%, at room temperature. The reaction was stirred under magnetic stirring for 4 h. After adding 27.5g (0.515mol) of ammonium chloride into the above system, the reaction was continued at room temperature for 48h. TLC tracks the end point of the reaction. After the reaction, the solvent is evaporated to dryness. The remaining solid is washed with diethyl ether, filtered, and repeated three times. The filter cake is sequentially recrystallized with hot water (about 60°C) and ethanol to obtain orange needle-like crystals of 3-nitrobenzene. Amidine hydrochloride 78g. Yield 77.4%.
Step 2,
3-Nitrobenzamidine dihydrochloride is prepared by reduction with hydrogen.
Apply[3]
WO2010054398 reported that 3-aminobenzamidine dihydrochloride can be used to prepare a type of ATR kinase inhibitor, as shown in the figure below. ATR has been implicated as a key component of the DDR in response to disrupted DNA replication. As a result, these cancer cells are more dependent on ATR activity for survival than healthy cells. Therefore, ATR inhibitors can be used in cancer therapy, either alone or in combination with DNA damaging agents, because they terminate DNA repair mechanisms that are more important for cell survival in many cancer cells than in healthy normal cells. important. Indeed, ATR inhibition has been shown to be effective in cancer cells both as a single agent and as a potent sensitizer for radiotherapy and genotoxic chemotherapy. There is a need to develop effective and selective ATR inhibitors to treat these diseases. More specifically, there is a need for the development of potent and selective ATR inhibitors for the treatment of cancer as single agents or as combination therapy with radiotherapy or genotoxic chemotherapy.
Main reference materials
[1] [Chinese invention, Chinese invention authorization] CN201010107499.8 5-amino-1,2,4-thiadiazole compounds and preparation method thereof
[2] Rogana, Edyr et al .Substituent effects on the pKa values of meta- and para-substituted benzamidinium ions , Journal of Chemical Research, Synopses, (9), 286-7; 1985
[3] (WO2010054398) COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE
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