CN108707080A - 一种利奈唑胺及其中间体的环保合成方法 - Google Patents

一种利奈唑胺及其中间体的环保合成方法 Download PDF

Info

Publication number
CN108707080A
CN108707080A CN201810637576.7A CN201810637576A CN108707080A CN 108707080 A CN108707080 A CN 108707080A CN 201810637576 A CN201810637576 A CN 201810637576A CN 108707080 A CN108707080 A CN 108707080A
Authority
CN
China
Prior art keywords
compound
formula
silicon substrate
linezolid
bromine
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201810637576.7A
Other languages
English (en)
Other versions
CN108707080B (zh
Inventor
王北朝
崔兴周
李广侠
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shanghai Shengying Biotechnology Co.,Ltd.
Original Assignee
Hefei Ling Ning Technology Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hefei Ling Ning Technology Co Ltd filed Critical Hefei Ling Ning Technology Co Ltd
Priority to CN201810637576.7A priority Critical patent/CN108707080B/zh
Publication of CN108707080A publication Critical patent/CN108707080A/zh
Application granted granted Critical
Publication of CN108707080B publication Critical patent/CN108707080B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
    • C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C215/04—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated
    • C07C215/06—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic
    • C07C215/08—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic with only one hydroxy group and one amino group bound to the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D203/00—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D203/04—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D203/06—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D203/08—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D263/18—Oxygen atoms
    • C07D263/20—Oxygen atoms attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/10—Compounds having one or more C—Si linkages containing nitrogen having a Si-N linkage
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

本发明涉及一种更加环保的利奈唑胺及其关键中间体的合成法，以天然手性产物L‑丝氨酸为起始原料，经羟基保护、羧基还原、羟基卤化、关环、羟基脱保护后卤化、开环等步骤制备得到利奈唑胺关键中间体。本发明提供的合成方法采用天然手性产物引入手性中心，反应收率高，工艺操作简单，产物纯度高，更加环保适合工业化生产。

Description

一种利奈唑胺及其中间体的环保合成方法
技术领域
本发明涉及一种制备噁唑烷酮抗菌剂的方法，具体涉及一种制备利奈唑胺及其中间体的方法。
背景技术
利奈唑胺作为一种人工合成的噁唑烷酮类抗生素，其结构新颖、作用机制独特、无交叉耐药性，用于治疗革兰阳性(G+)球菌引起的感染，包括由耐甲氧西林金黄色葡萄球菌(MRSA)引起的疑似或确诊院内获得性肺炎(HAP)、社区获得性肺炎(CAP)、复杂性皮肤或皮肤软组织感染(SSTI)以及耐万古霉素肠球菌(VRE)感染。
文献《化学与生物工程》vol.30.NO.1，57-59(2013)公开了制备利奈唑胺的方法，其合成路线如下：
文献《Org.process Res Dev》7(4):533-546公开了制备利奈唑胺的方法。其路线如下：
专利CN101415694A中描述了一种由氯醇和氨基甲酸酯制备利奈唑胺的方法，其合成路线如下：
以上合成路线均采用手性环氧氯丙烷或手性环氧丙烷衍生物引入手性中性，合成路线步骤长，而且反应过程中需要深冷等反应条件，反应收率低，成本较高，对环境的污染较大。
发明内容
本发明采用L-丝氨酸为起始原料，经羟基保护、羧基还原、羟基卤化、关环、羟基脱保护后卤化、开环等步骤合成利奈唑胺关键中间体式Ⅶ化合物，合成路线如下：
其中，R1为羟基保护基，X为卤素，Y为卤素。
本发明的实施方案中，R1选自硅烷基；R1还可以选自三甲基硅基、三乙基硅基、三异丙基硅基、二甲基异丙基硅基、二乙基异丙基硅基、叔丁基二甲基硅基、叔丁基二苯基硅基、三苄基硅基、三对甲苯基硅基、三苯基硅基、二苯基甲基硅基、二叔丁基甲基硅基或三(三甲基硅基)硅基。
本发明的实施方案中，X或Y独立的选自氯或溴。
本发明步骤2使用的还原剂选自氢化铝锂或硼氢化钠/碘；步骤3使用的卤化剂选自三苯基膦/NCS或三苯基膦/NBS。
本发明还提供用于制备利奈唑胺的关键中间体式Ⅵ所示化合物，
其中，Y选自氯或溴。
本发明还提供用于制备利奈唑胺的关键中间体式Ⅶ所示化合物，
其中，Y选自氯或溴。
本发明还提供一种利奈唑胺的制备方法，将本发明制备的式Ⅶ化合物经乙酰基保护得式Ⅷ化合物，式Ⅷ化合物与式Ⅸ化合物反应得利奈唑胺，
，其中，Y选自氯或溴。
与现有技术相比，本发明提供的合成方法采用天然手性产物引入手性中心，反应收率高，工艺操作简单，产物纯度高，更加环保适合工业化生产。
具体实施方式
下面将结合具体实施例，对本发明的实施方案进行详细描述。以下实施例仅用于说明本发明，而不应视为限定本发明的范围。
实施例1
在反应瓶中加入L-丝氨酸105g，DMF 500ml，冰水浴冷却至0℃，加入咪唑80g，分批缓慢加入TBSCl 157g，加完后升至室温搅拌16小时。加入水500ml淬灭反应，减压浓缩回收大部分溶剂，加入水500ml、二氯甲烷500ml萃取，合并有机相，无水硫酸钠干燥、浓缩得到中间体2210g，收率95.9％，MS：220.13[M+H+]。
实施例2
三口瓶中加入中间体2219g、四氢呋喃1L、甲醇100mL，冰盐浴冷却至0-5℃左右，加入硼氢化钠40g，加毕滴加碘127g的四氢呋喃溶液100ml，滴毕将反应体系的温度升到回流，并继续搅拌反应2小时，TLC检测原料反应完毕后，饱和氯化铵水溶液500ml淬灭反应，减压蒸馏，残留物用乙酸乙酯(300mL×2)萃取，有机相依次用饱和碳酸氢钠水溶液和盐水洗，无水硫酸钠干燥后浓缩，中间体3200g，收率97.5％，MS：206.37[M+H+]。
实施例3
反应瓶中加入上述中间体3205g、二氯甲烷1L，冷却至0℃下加入三苯基磷390g、NBS 267g，加完毕升至室温搅拌4小时，加入水1L淬灭反应，静置分液，有机相再用饱和食盐水500mL洗涤，有机层用无水硫酸钠干燥、过滤、浓缩，得到中间体4，中间体4粗产品不经纯化直接用于下一步反应。
实施例4
将实施例3所得中间体4粗产品加入四氢呋喃500ml中，0℃下分批加入60％氢化钠40g，搅拌反应15分钟后，加入饱和氯化铵溶液500ml淬灭反应，用乙酸乙酯500mL萃取，有机相用饱和食盐水洗涤，无水硫酸钠干燥、过滤、浓缩，得到中间体5，中间体5粗产品不经纯化直接用于下一步反应。
实施例5
将实施例4所得中间体5粗产品加入四氢呋喃500ml中，加入TBAF 350g，室温下反应于2小时，减压浓缩回收四氢呋喃，残留物用乙酸乙酯500mL溶解后，用饱和食盐水500ml洗涤2两次，无水硫酸钠干燥、过滤、浓缩得中间体6，中间体6粗产品不经纯化直接用于下一步反应。
将上部所得中间体6加入二氯甲烷600mL，0℃加入三苯基磷300g、四氯化碳230g，加完毕升至室温搅拌4小时，加入水600mL，静置分液，有机相再用饱和食盐水500mL洗涤，干燥、过滤、浓缩，柱层析纯化得到中间体775g，四步反应总收率为82.4％，HPLC检测纯度99.5％，光学纯度100.0％，MS：92.02、94.02[M+H+]。
实施例6
反应瓶中加入上述中间体791.5g、四氢呋喃1L，15～20℃加入加入1mol/L盐酸水溶液30ml，搅拌反应20小时得中间体8四氢呋喃溶液。反应完毕，加入吡啶80g，升温至38～42℃，缓慢滴加醋酸酐120g，滴毕35-45℃继续搅拌反应12h。反应完毕，冷却至5-15℃，加入水500ml，滴加饱和K2CO3水溶液700ml溶液，二氯甲烷250mL萃取两次，有机层减压浓缩至干。加入正庚烷(2.0L)，搅拌1h，过滤，干燥，得产物为白色固体174g，两步反应总收率90.0％，HPLC检测纯度99.7％，光学纯度100.0％，MS：194.05、196.05[M+H+]。
实施例7
反应瓶中加入中间体(S)-1-乙酰氨基-2-乙酰氧基-3-氯丙烷100g、化合物Ⅷ120g，加入四氢呋喃200ml和甲醇25ml，降温至5℃，加入LiOtBu 72g的THF溶液200ml，室温反应16小时。冷却至0-10℃，滴加冰醋酸35mL，滴毕加入水400ml和二氯甲烷400mL，分液，水层以二氯甲烷200mL萃取。合并有机相，干燥，过滤。滤液减压浓缩回收溶剂得利奈唑胺83g，HPLC检测纯度99.9％，光学纯度100.0％，MS：338.14[M+H+]。

Claims (10)

1.一种利奈唑胺中间体式Ⅶ化合物的制备方法，包括以下步骤：
(1)、式Ⅰ化合物L-氨酸经羟基保护得式Ⅱ化合物,
(2)、式Ⅱ化合物羧基还原得式Ⅲ化合物,
(3)、式Ⅲ化合物羟基卤化得式Ⅳ化合物,
(4)、式Ⅳ化合物关环得式Ⅴ化合物,
(5)、式Ⅴ化合物羟基脱保护后卤化得式Ⅵ化合物,
(6)、式Ⅵ化合物开环得式Ⅶ化合物，
其中，R1为羟基保护基，X为卤素，Y为卤素。
2.根据权利要求1所述方法，其特征在于，R1为硅烷基。
3.根据权利要求1所述方法，其特征在于，R1选自选自三甲基硅基、三乙基硅基、三异丙基硅基、二甲基异丙基硅基、二乙基异丙基硅基、叔丁基二甲基硅基、叔丁基二苯基硅基、三苄基硅基、三对甲苯基硅基、三苯基硅基、二苯基甲基硅基、二叔丁基甲基硅基或三(三甲基硅基)硅基。
4.根据权利要求1所述方法，其特征在于，X选自氯或溴。
5.根据权利要求1所述方法，其特征在于，Y选自氯或溴。
6.根据权利要求1所述方法，其特征在于，步骤2使用的还原剂选自氢化铝锂或硼氢化钠/碘。
7.根据权利要求1所述方法，其特征在于，步骤3使用的卤化剂选自三聚氰氯或三苯基膦/NBS。
8.式Ⅵ所示化合物，其特征在于，Y选自氯或溴，
9.式Ⅶ所示化合物，其特征在于，Y选自氯或溴，
10.一种利奈唑胺的制备方法，其特征在于，权利要求1-5任一项制备的式Ⅶ化合物经乙酰基保护得式Ⅷ化合物，式Ⅷ化合物与式Ⅸ化合物反应得利奈唑胺，
其中，Y选自氯或溴。
CN201810637576.7A 2018-06-20 2018-06-20 一种利奈唑胺及其中间体的环保合成方法 Active CN108707080B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201810637576.7A CN108707080B (zh) 2018-06-20 2018-06-20 一种利奈唑胺及其中间体的环保合成方法

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201810637576.7A CN108707080B (zh) 2018-06-20 2018-06-20 一种利奈唑胺及其中间体的环保合成方法

Publications (2)

Publication Number Publication Date
CN108707080A true CN108707080A (zh) 2018-10-26
CN108707080B CN108707080B (zh) 2022-01-25

Family

ID=63871845

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201810637576.7A Active CN108707080B (zh) 2018-06-20 2018-06-20 一种利奈唑胺及其中间体的环保合成方法

Country Status (1)

Country Link
CN (1) CN108707080B (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110015969A (zh) * 2019-04-28 2019-07-16 梯尔希（南京）药物研发有限公司 一种利奈唑胺杂质的合成方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013046211A1 (en) * 2011-09-27 2013-04-04 Symed Labs Limited Processes for the preparation of 5-chloro-n-({(5s)-2-oxo-3-[4-(3-oxo-4-morpholinyl) phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophene-carboxamide and intermediates thereof
US20150299160A1 (en) * 2012-04-16 2015-10-22 Ranbaxy Laboratories Limited Process for the preparation of rivaroxaban and intermediates thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013046211A1 (en) * 2011-09-27 2013-04-04 Symed Labs Limited Processes for the preparation of 5-chloro-n-({(5s)-2-oxo-3-[4-(3-oxo-4-morpholinyl) phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophene-carboxamide and intermediates thereof
US20150299160A1 (en) * 2012-04-16 2015-10-22 Ranbaxy Laboratories Limited Process for the preparation of rivaroxaban and intermediates thereof

Non-Patent Citations (11)

* Cited by examiner, † Cited by third party
Title
BONGINI, ALESSANDRO等: "Iodocyclofunctionalization of (Z)-1-trichloroacetimidoyloxyalk-2-enes and 3-trichloroacetimidoyloxyalk-1-enes. Synthesis of (±)-erythro-sphinganine triacetate and (±)-threo-sphinganine triacetate", 《JOURNAL OF THE CHEMICAL SOCIETY, PERKIN TRANSACTIONS 1: ORGANIC AND BIO-ORGANIC CHEMISTRY》 *
CHEMICAL ABSTRACT RN: "RN：694432-99-0", 《STN ON THE WEB REGISTRY数据库》 *
CHOI, JUN YOUNG等: "Highly Efficient Synthesis of Enantiomerically Enriched 2-Hydroxymethylaziridines by Enzymatic Desymmetrization", 《ORGANIC LETTERS》 *
D"HOOGHE, MATTHIAS等: "New Synthesis of Propargylic Amines from 2-(Bromomethyl)aziridines. Intermediacy of 3-Bromoazetidinium Salts", 《JOURNAL OF ORGANIC CHEMISTRY》 *
DOU, XIAO-YONG等: "Catalyst-free process for the synthesis of 5-aryl-2-oxazolidinones via cycloaddition reaction of aziridines and carbon dioxide", 《SYNLETT》 *
KISSMAN, HENRY M.等: "2,2-Diphenyl-3,3-dimethylethylenimine and Related Compounds", 《JOURNAL OF THE AMERICAN CHEMICAL SOCIETY》 *
LI, KANGYING等: "Synthesis of several chiral phosphinamides and their application in the asymmetric borane reduction of prochiral ketones", 《MAIN GROUP METAL CHEMISTRY》 *
SHCHERBATIUK, ANDRIY V.等: "Synthesis of 2- and 3-trifluoromethylmorpholines: useful building blocks for drug discovery", 《TETRAHEDRON》 *
WILLIAM R. PERRAULT等: "The Synthesis of N-Aryl-5(S)-aminomethyl-2-oxazolidinone Antibacterials and Derivatives in One Step from Aryl Carbamates", 《ORGANIC PROCESS RESEARCH & DEVELOPMENT》 *
XU, WENJIN等: "Asymmetric borane reduction of prochiral ketones catalyzed by α,α-disubstituted aziridinemethanols", 《CATALYSIS LETTERS》 *
吴亚弟: "新型抗菌药利奈唑胺合成工艺的改进", 《工程科技Ⅰ辑》 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110015969A (zh) * 2019-04-28 2019-07-16 梯尔希（南京）药物研发有限公司 一种利奈唑胺杂质的合成方法

Also Published As

Publication number Publication date
CN108707080B (zh) 2022-01-25

Similar Documents

Publication Publication Date Title
CN105102425B (zh) 制备胆汁酸衍生物的方法
CN108047261A (zh) 一种克立硼罗的制备方法
CN103965280B (zh) 一种氟维司群中间体的制备方法
JPS6032799A (ja) 新規４′−デメチル−４−エピポドフィロトキシン誘導体
WO2015158191A1 (zh) 一种立体选择性的合成降血脂药物依折麦布的方法
CN107311875A (zh) 重酒石酸间羟胺的合成方法
CN108707080A (zh) 一种利奈唑胺及其中间体的环保合成方法
CN110305118A (zh) 一种适合工业生产恩格列净的合成方法
CN110183445A (zh) 莫西沙星及其衍生物的合成方法
CN107652277A (zh) 一种依帕列净的制备方法
CN108341738B (zh) 用于制备艾日布林的方法及其中间体
CN106432388A (zh) (2’r) ‑2’‑脱氧‑2’‑氟‑ 2’‑甲基脲苷的制备方法
CN106588739B (zh) 一种反-3-羟基-l-脯氨酸制备方法
CN111170893A (zh) Lefamulin的中间体化合物及其在Lefamulin制备中的应用
CN103058907B (zh) 鲁比前列酮或其中间体的制备方法
CN103360297A (zh) 一种反-3-羟基-l-脯氨酸的制备方法
CN107200763A (zh) 一种以鹅去氧胆酸为原料合成石胆酸的方法
CN107216332A (zh) 叔丁基‑7‑羟甲基‑7,8‑二氢4h吡唑并二氮杂卓5(6h)甲酸基酯的合成方法
CN107011377A (zh) 一种β‑羰基磷酸酯的制备方法
CN107722042B (zh) 一种氟氧头孢母核的合成方法
CN110551063A (zh) 一种合成5-(n-boc-哌嗪-1-基)吡啶-2-胺的方法
CN110698529A (zh) 一种依普利酮中间体△9,11烯酯的制备方法
JP5265144B2 (ja) ３−ｏ−置換−カテキン類誘導体の新規製造方法
Gurjar et al. A synthesis of 1, 5-di-O-acetyl-3-azido-2, 3-dideoxy-D-ribofuranose
CN104592253B (zh) 一种替西罗莫司的新合成方法

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
TA01 Transfer of patent application right

Effective date of registration: 20210121

Address after: 102600 unit 3, building 37, Zhongli, Huangcun Town station, Daxing District, Beijing

Applicant after: Xie Yongqin

Address before: 230000 north of Danxia Road, west of feicui Road, Hefei Economic and Technological Development Zone, Hefei City, Anhui Province

Applicant before: HEFEI LINGNING TECHNOLOGY Co.,Ltd.

TA01 Transfer of patent application right
TA01 Transfer of patent application right

Effective date of registration: 20211229

Address after: 201400 Building 5, 936 Guoshun Road, Nanqiao Town, Fengxian District, Shanghai

Applicant after: Shanghai Shengying Biotechnology Co.,Ltd.

Address before: 102600 unit 3, building 37, Zhongli, Huangcun Town station, Daxing District, Beijing

Applicant before: Xie Yongqin

TA01 Transfer of patent application right
GR01 Patent grant
GR01 Patent grant