A method of preparing and intermediates thereof linagliptin

The present invention belongs to the field of pharmaceutical chemistry, specifically relates to a method for preparing intermediate and linagliptin, compound Ⅰ and 2-butyn-1-ol, at a trialkylphosphine, an azo reagent presence of an organic solvent Mitsunobu reaction occurs, to give an intermediate compound linagliptin ⅱ; compound ⅱ and (R) -3- aminopiperidine, isopropanol as the solvent, acid binding agent as tributylamine substitution reaction, to give compound ⅲ; ⅲ 4--2-chloro compound and - methylquinazolin-alkylation reaction occurs, to give linagliptin. Mitsunobu reaction using compound was prepared according to the present invention is innovative Ⅱ, mild reaction conditions, reasonable operation, high selectivity, product quality advantages. And by controlling the reaction conditions, with a compound R-3- Ⅲ-aminopiperidine or an inorganic or organic acid salts, direct nucleophilic substitution reaction to produce linagliptin, without protection and deprotection of the amino group method, reducing the reaction steps, the reaction process easier, the cost is reduced, and the resulting purity also increased.