公开(公告)号：US20180194753A1

公开(公告)日：2018-07-12

申请号：US15737483

申请日：2016-06-15

申请人： ZHEJIANG YONGTAI TECHNOLOGY CO., LTD

发明人： Hongming SHAO ,  Renbao HE ,  Yizhong JIN ,  Lei WANG

IPC分类号： C07D405/04 ,  C07D231/14 ,  C07C251/12 ,  C07C251/14

CPC分类号： C07D405/04 ,  C07B33/00 ,  C07C49/255 ,  C07C221/00 ,  C07C225/14 ,  C07C251/12 ,  C07C251/14 ,  C07D231/12 ,  C07D231/14 ,  C07D251/30 ,  C07D295/125

摘要： Provided are a preparation method for synthesizing a pyrazolecarboxylic acid derivative of the following formula (I), which is suitable for industrial production, and an intermediate as shown by the following formula (II). The method is high in reaction yield in each step, low in waste gas and waste water and low in cost, and requires no special reaction equipment.

公开(公告)号：US20220396816A1

公开(公告)日：2022-12-15

申请号：US17778627

申请日：2021-01-21

申请人： ZHEJIANG YONGTAI TECHNOLOGY CO., LTD. ,  ZHEJIANG UNIVERSITY OF TECHNOLOGY ,  ZHEJIANG YONGTAI PHARMACEUTICAL CO., LTD.

发明人： Zhiqiang LIU ,  Feng CHENG ,  Xiaojian ZHANG ,  Dongxu JIA ,  Yuguo ZHENG ,  Renbao HE ,  Yizhong JIN ,  Hongming SHAO ,  Jiaohua LIN ,  Feng ZHANG

IPC分类号： C12P17/18 ,  C12N9/10 ,  C12N1/20 ,  C12N15/70

摘要： The present invention discloses a transaminase mutant and application thereof in preparation of sitagliptin intermediates, the transaminase mutant is obtained by substitution of tyrosine with proline at position 74, substitution of glutamic acid with aspartic acid at position 228, substitution of leucine with alanine at position 254 and substitution of methionine with threonine at position 290 of the amino acid sequence shown in SEQ ID NO: 2. The present invention uses wet cells or a purified transaminase as a biocatalyst and a sitagliptin precursor ketone or a prochiral carbonyl compound as a substrate to prepare a sitagliptin intermediate or a sitagliptin ester intermediate; the total yield of the method reaches about 82%, and e.e. value of the product reaches 99%.

公开(公告)号：US20190202791A1

公开(公告)日：2019-07-04

申请号：US16325717

申请日：2016-09-29

申请人： ZHEJIANG YONGTAI TECHNOLOGY CO., LTD.

发明人： Renbao HE ,  Yingmei WANG ,  Hongming SHAO ,  Yizhong JIN

IPC分类号： C07D231/28

摘要： The present invention relates to a method for synthesizing a compound of 3-(difluoromethyl)-1-methyl-1h-pyrazole-4-carboxylic acid, wherein including the steps of: (A) the diethyl ester compounds represented by the following Formula IV are reacted under the action of amine, alkali and carbonyl reagents to produce the acrylic diester compound represented by the following Formula I, wherein (B) the above compound represented by the Formula I is reacted with a fluoride reagent, a Lewis acid and a methyl hydrazine to form a pyrazole ring-containing diester compound represented by the Formula II, (C) the heterocyclic-containing diester compound represented by the Formula II is reacted with a base to give 3-(difluoromethyl)-1-methyl-1h-pyrazole-4-carboxylic acid represented by the Formula III.