The invention generally relates to compounds having structure I: ##STR00001## wherein x represents alkyl, aryl or het-aryl, each of y independently represents hydrogen or halogen and z represents hydrogen or alkyl. Further, said compounds are inhibitors of MEK 1, 2 and 5. Furthermore, the invention includes methods of making said compounds, compositions including said compounds and uses for inhibiting MEK 1, 2 and 5.

A method for continuous-flow amination for an alkyl carboxylic acid compound is provided, in which an amination reagent and a catalyst are mixed in a first micro-mixer and then preheated in a preheater. The mixture is mixed with a substituted alkyl carboxylic acid solution in a second micro-mixer and reacted in a dynamic flow reactor to produce a mixture including a carboxyl-containing organic amine product. Then, the mixture is subjected to gas-liquid separation, and the liquid phase is collected and filtered to obtain a first filtrate and a first filter residue. The first filter residue is mixed with a base solution under stirring and filtered to obtain a second filtrate and a second filter residue. The second filter residue was dried to yield a high-purity carboxyl-containing organic amine product.

A method for continuous-flow amination for an alkyl carboxylic acid compound is provided, in which an amination reagent and a catalyst are mixed in a first micro-mixer and then preheated in a preheater. The mixture is mixed with a substituted alkyl carboxylic acid solution in a second micro-mixer and reacted in a dynamic flow reactor to produce a mixture including a carboxyl-containing organic amine product. Then, the mixture is subjected to gas-liquid separation, and the liquid phase is collected and filtered to obtain a first filtrate and a first filter residue. The first filter residue is mixed with a base solution under stirring and filtered to obtain a second filtrate and a second filter residue. The second filter residue was dried to yield a high-purity carboxyl-containing organic amine product.