- Traceless Staudinger ligation enabled parallel synthesis of proteolysis targeting chimera linker variants
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A parallel, one-pot assembly approach to proteolysis targeting chimeras (PROTACs) is demonstrated utilizing activated esters generatedin situ, and traceless Staudinger ligation chemistry. The method described allows for rapid structure-activity relationship studies of PROTAC linker variants. Two previously studied systems, cereblon and BRD4 degraders, are examined as test cases for the synthetic method. The two related strategies to assemble PROTAC linker variants discussed can accommodate the chromotographic separations capabilities of labs of many sizes and incorporates commercially available degrader building blocks, thereby easing synthetic entry into PROTAC chemical space.
- Bemis, Troy A.,La Clair, James J.,Burkart, Michael D.
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supporting information
p. 1026 - 1029
(2021/02/06)
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- Synthesis method of pomalidomide intermediate
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The invention relates to a synthesis method of a pomalidomide intermediate, and especially relates to a synthesis method of a pomalidomide key intermediate 3-aminopiperidine-2, 6-dione hydrochloride.The method comprises the following steps: reacting a raw material L-glutamic acid with ammonia water to generate diammonium salt of L-glutamic acid, removing monomolecular ammonia gas from the diammonium salt of L-glutamic acid to cyclize to generate 3-aminopiperidine-2, 6-dione, dissolving the 3-aminopiperidine-2, 6-dione in ethanol, introducing hydrochloric acid gas into the system, filtering, and drying to obtain 3-aminopiperidine-2, 6-dione hydrochloride. Toxic and harmful substances are not used in the reaction, and the single-step reaction is simple and easy to carry out.
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Paragraph 0009; 0028-0043
(2020/09/30)
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- Preparation method of lenadomide
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The invention discloses a preparation method of lenalidomide, and belongs to the field of organic synthesis. 2-methyl-3-methyl nitrobenzoate and 3-N-benzyloxy-carbonyl-L-glutamine serve as starting materials, and an important intermediate 2-brooethyl-3-methyl nitrobenzoate is obtained through a bromination reaction of 2-methyl-3-methyl nitrobenzoate. 3-N-benzyloxy-carbonyl-L-glutamine is cyclizedunder catalysis to produce 3-N-benzyloxy-carbonyl-2,6-dioxopiperidine, an amino group is subjected to deprotection to produce 3-amino-2,6-piperidone halide, 3-(4-nitro-1-oxo-1,3-o-xylylenimine-2-yl)piperidine-2,6-diketone is obtained through an aminolysis reaction of 3-N-benzyloxy-carbonyl-2,6-dioxopiperidine and 2-brooethyl-3-methyl nitrobenzoate, and then lenalidomide is prepared through reduction. The method has the advantages that the cost of raw materials are low, aftertreatment is simple, and the yield is high, and the production cost of the lenalidomide as a bulk drug is greatly reduced. The method is a convenient and efficient lenalidomide synthesis method suitable for industrial production.
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Paragraph 0037-0038
(2019/06/07)
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- A method for the preparation of amine to that (by machine translation)
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The invention discloses a method for the preparation of amine to that, the specific step includes: to 2 - methyl - 3 - nitro benzoic acid as the raw material, to obtain 2 - bromomethyl - 3 - nitro-benzoic acid methyl ester; L - glutamic acid as the raw material to make the N - CBZ - L - glutamic acid; to N - CBZ - L - glutamic acid as the raw material to make the 3 - amino - 2, 6 - piperidine dione hydrochloride; to 2 - methyl - 3 - nitro-benzoic acid methyl ester with 3 - amino - 2, 6 - piperidine dione hydrochloride as the raw material to make the 3 - (4 - nitro - 1, 3 dihydro - 1 - oxo - 2 hydrogen - isoindol - 2 - yl) piperidine - 2, 6 - dione; to 3 - (4 - nitro - 1, 3 dihydro - 1 - oxo - 2 hydrogen - isoindol - 2 - yl) piperidine - 2, 6 - dione as raw materials to that amine. The method of the invention has simple technological process, raw material economic, few by-products, and purification is simple, high yield, environment-friendly and the like, after treatment is simple, has better practicability and application value, has great industrial prospects. (by machine translation)
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- PROCESS FOR THE PREPARATION OF POMALIDOMIDE
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The present invention relates to a process for the preparation of pomalidomide. The present invention also provides a process for the preparation of 2-(2,6-dioxopiperidin-3-yl)-4-nitro-1H-isoindole-1,3(2H)-dione, a compound of Formula II and its use for the preparation of pomalidomide. The pomalidomide may be made having a yield greater than 97% and the 2-(2,6-dioxopiperidin-3-yl)-4-nitro-1H-isoindole-1,3(2H)-dione (Formula II) may be made having a yield greater than 88%.
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Page/Page column 7-8
(2018/09/19)
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- ACID ADDITION SALTS OF LENALIDOMIDE
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The invention relates to acid addition salts of lenalidomide as well as to desirable polymorphic forms of lenalidomide hydrogen sulfate. Furthermore, the invention provides a process for producing acid addition salts of lenalidomide, which optionally can comprise a further step producing lenalidomide in form of the free base.
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Page/Page column 30-31
(2011/05/11)
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- (2,6-DIOXO-3-PIPERINYL)AMIDOBENZOIC IMMUNOMODULATORY AND ANTI-CANCER DERIVATIVES
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The present invention is concerned with certain benzoic acid derivatives and their use in the treatment of neoplastic disorders and as immune modulators. In particular the present invention is concerned with carboxybenzoyl glutamic acid analogues and their uses.
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Page/Page column 13
(2010/11/29)
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- Amino-substituted thalidomide analogs: Potent inhibitors of TNF-α production
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Thalidomide, (1), is a known inhibitor of TNF-α release in LPS stimulated human PBMC. Herein we describe the TNF-α inhibitory activity of amino substituted analogs of thalidomide (1) and its isoindolin-1-one analog, EM-12 (2). The 4-amino substituted analogs were found to be potent inhibitors of TNF-α release in LPS stimulated human PBMC.
- Muller, George W.,Chen, Roger,Huang, Shaei-Yun,Corral, Laura G.,Wong, Lu Min,Patterson, Rebecca T.,Chen, Yuxi,Kaplan, Gilla,Stirling, David I.
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p. 1625 - 1630
(2007/10/03)
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