A kind of method of multiphase duplex continuous production and preparation of vildagliptin

Abstract

The invention discloses a method for preparing vildagliptin by multiphase duplex continuous production. In the acid chloride solution, the reaction is carried out, the reaction solution is not treated, a dehydrating agent is added, quenched, the pH value is adjusted to neutrality, the organic layer is layered and added dropwise to the amantadine alcohol solution, the temperature is controlled and kept warm, concentrated, pulped, and filtered. , washing the filter cake, and drying to obtain vildagliptin. In the present invention, 2,6-lutidine is also used as a solvent as an acid binding agent, and the addition of amantadine is carried out under homogeneous conditions without generating solids, and the reaction solution is directly used to carry out the next step reaction. The stirring requirement is low; while the post-processing steps are reduced, the energy consumption is reduced and the yield is improved; the commercial production can be more realized; the time is shortened, the post-processing is simple, and the operating conditions are simple.

Description

technical field

[0001] The present invention relates to the field of preparation methods of vildagliptin. More specifically, the present invention relates to a method for preparing vildagliptin by multiphase duplex continuous production. Background technique

[0002] The clinical drug vildagliptin is another orally administered dipeptidyl peptidase-IV (DPP-IV) inhibitor after sitagliptin. , was approved for marketing in the European Union in 2008 for the treatment of type 2 diabetes. Vildagliptin is a selective, competitive and reversible DPP24 inhibitor.

[0003] But in general, the reaction route for synthesizing vildagliptin is long, the reaction is cumbersome, the reaction is carried out under two-phase conditions, and the production equipment is required to be high, so the energy consumption is large, the yield is low, the reaction time is long, and the follow-up treatment It is complicated and has high operating conditions, which is not conducive to the realization ...