- Process development of an N-benzylated chloropurine at the kilogram scale
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A two-step pharmaceutical manufacturing process was developed for the large-scale preparation of 6-chloro-9-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-9H-purin-2-amine methanesulfonic acid salt (4) from commercially available starting materials. In the first step, the benzylpurine free base (3) was prepared by benzylation of 6-chloro-9H-purin-2-amine (1) with 2-(chloromethyl)-4-methoxy-3,5-dimethylpyridine hydrochloride (2). The benzylpurine free base was then directly converted into the methanesulfonic acid salt. It was necessary to charge the pyridine hydrochloride 2 in portions into the mixture of K2CO3 (-325 mesh) and the chloropurine compound 1 in dimethylacetamide (DMA). The major regioisomeric impurity (6), formed by N7 benzylation, and inorganic salts were removed by filtration. Treatment of the DMA filtrate with MsOH afforded the target salt with negligible degradation. In the second step, recrystallization of the crude salt from DMSO-EtOAc with seeding gave crystalline API in high yield and purity despite the hydrolytic instability of the product in solution.
- Shi, Xianglin,Chang, Hexi,Grohmann, Markus,Kiesman, William F.,Kwok, Daw-Iong Albert
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Read Online
- O nitroaryloxy acylated derivative compounds, preparation method and application thereof (by machine translation)
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The invention discloses a formula shown adjacent nitroaryloxy acylated derivative compounds, and this compound A preparation method and use thereof. The invention adjacent nitroaryloxy acylated derivative compounds can be used for preparing HSP90 inhibitor drugs, in particular the preparation of anti-tumor drug, and has higher selectivity of tumor cells, to the organism the advantage of small toxicity. (by machine translation)
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Paragraph 0025; 0026
(2018/04/28)
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- A O-nitroaryloxy acylated derivative compounds, preparation method and application thereof (by machine translation)
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The invention discloses a such as [...] nitroaryloxy acylated derivative compounds, and this method for preparing compound and use thereof. The invention adjacent nitroaryloxy acylated derivative compounds can be used for preparing HSP90 Inhibitor drugs, in particular the preparation of anti-tumor drug, and has higher selectivity of tumor cells, to the organism the advantage of small toxicity. (by machine translation)
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Paragraph 0014-0016
(2018/04/21)
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- NOVEL HETEROCYCLIC COMPOUNDS AS HSP90-INHIBITORS
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Novel heterocyclic compounds are described and demonstrated to have utility as Heat Shock Protein 90 (HSP90) inhibiting agent. Method of synthesis and use of such compounds are also described.
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Page/Page column 303
(2008/06/13)
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