- Process Development Overcomes a Challenging Pd-Catalyzed C-N Coupling for the Synthesis of RORc Inhibitor GDC-0022
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Process development for a multi-kilogram-scale synthesis of GDC-0022, an inhibitor of retinoic acid receptor-related orphan receptor γ(RORc), is described. Delivery of the active pharmaceutical ingredient (API) relied on diastereoselective preparation of a six-membered sultam building block, as well as execution of its benzylation under heterogeneous conditions. Investigation and optimization of a challenging late-stage palladium-catalyzed C-N coupling of a bicyclic amine were likewise central to synthetic efforts. Understanding of this key reaction, as well as the development of API salt forms and isolations, ultimately enabled a successful reaction at 8.0 kg scale, utilizing 1.0 mol % XantPhos-Pd-G2 as precatalyst and, in turn, preparation of >5.0 kg of GDC-0022 tosylate salt for preclinical needs.
- Sirois, Lauren E.,Lao, David,Xu, Jie,Angelaud, Rémy,Tso, Jerry,Scott, Brandon,Chakravarty, Paroma,Malhotra, Sushant,Gosselin, Francis
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- Triazole derivative with tumor cell calcium ion channel and preparation method and application thereof
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The invention relates to the technical field of pharmaceutical chemistry synthesis, in particular to a triazole derivative with a tumor cell calcium ion channel and a preparation method and application thereof. By click reaction, benzyl in the structure is changed to 1, 2 and 3 - triazole structures to obtain a novel compound, can inhibit growth of tumor cells by influencing calcium ion channels in tumor cells, and has remarkable application value.
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Paragraph 0126-0128
(2021/10/27)
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- Method for preparing (R)-3-aminobutanol
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The invention provides a method for preparing (R)-3-aminobutanol, and the method comprises the following steps of: (1) providing 4-hydroxy-2-butanone and carrying out ammoniation reduction on the 4-hydroxy-2-butanone to obtain racemic 3-aminobutanol; (2) reacting (S)-mandelic acid with the racemic 3-aminobutanol to obtain resolved mandelic acid salt; and (3) alkalizing the resolved mandelic acid salt to obtain the product (R)-3-aminobutanol. According to the invention, the process of preparing the (R)-3-aminobutanol through reductive amination and salification resolution is simple and convenient to operate, low in reaction danger and pollution; the purity of the obtained (R)-3-aminobutanol reaches 99.9% (GC method).
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Paragraph 0068-0077
(2020/01/25)
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- Synthetic method of dolutegravir key intermediate (R)-3-aminobutanol
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The invention discloses a synthetic method of dolutegravir key intermediate (R)-3-aminobutanol. The synthesis route is disclosed in the invention, and is suitable for industrialized large-scale production of (R)-3-aminobutanol; product optical purity is increased effectively; using of raw materials dangerous in operation is avoided; product yield is extremely high; and the synthetic method is suitable for industrialized popularization and application.
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Paragraph 0033; 0034
(2017/08/29)
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- SEPARATION OF AN ENANTIOMER MIXTURE OF (R)- AND (S)-3-AMINO-1-BUTANOL
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The present invention relates to a process for separating an enantiomer mixture of (R)- and (S)-3-amino-1-butanol optionally protected on the oxygen atom, and to a process for preparing essentially enantiomerically pure (R)-3-amino-1-butanol which optionally bears a protecting group on the oxygen atom.
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Page/Page column 6
(2011/11/13)
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