Novel epidermal growth factor receptor inhibitor and application thereof
A technology of use and carrier, applied in the field of drug resistance inhibitors and novel epidermal growth factor receptor inhibitors, which can solve the problems of difficult to achieve concentration and drug resistance.
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Embodiment 1
[0118] Embodiment 1 compound preparation
[0119]
[0120] Intermediate A and N,N,N'-trimethylaminoethyl-1,2-diamine (B) were dissolved in n-butanol, DIPEA was added, and the mixture was stirred overnight in an oil bath at 130°C. with SiO 2 After absorbing the mixed solution, a solid C was separated by column chromatography.
[0121] The solid C, ammonium chloride and iron powder were refluxed and stirred in the mixture of ethanol and water for 2 hours, and the intermediate D was separated by column chromatography.
[0122] Dissolve the intermediate D, DIPEA in dichloromethane cooled in an ice bath, then slowly add the corresponding acid chloride dropwise, and stir until the reaction is complete. Pour into NaHCO 3 solution, extracted with dichloromethane, and purified by silica gel column chromatography to obtain Compound E.
Embodiment 2
[0123] Embodiment 2 compound preparation
[0124]
[0125] Intermediates A and H were dissolved in n-butanol, DIPEA was added, and the mixture was stirred overnight in an oil bath at 130°C. with SiO 2 After absorbing the mixed solution, a solid I was separated by column chromatography.
[0126] The solid C, ammonium chloride and iron powder were refluxed and stirred in the mixture of ethanol and water for 2 hours. The intermediate J was separated by column chromatography.
[0127] The intermediate J, DIPEA was dissolved in dichloromethane cooled in an ice bath, and then the corresponding prepared acid chloride was slowly added dropwise, and stirred until the reaction was complete. Pour into NaHCO 3 solution, extracted with dichloromethane, and purified by silica gel column chromatography to obtain Compound K.
Embodiment 3
[0128] Example 3 compound preparation
[0129]
[0130] The intermediate J, DIPEA was dissolved in dichloromethane cooled in an ice bath, and then the corresponding prepared acid chloride was slowly added dropwise, and stirred until the reaction was complete. Pour into NaHCO 3 solution, extracted with dichloromethane, and purified by silica gel column chromatography to obtain Compound L.
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