- Preparation method of N-benzyl-3-oxopiperidine-4-carboxylic acid ethyl ester hydrochloride
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The invention provides a preparation method of N-benzyl-3-oxopiperidine-4-carboxylic acid ethyl ester hydrochloride, and the method comprises the following steps: (1) preparing an intermediate 2: dissolving N-benzyl glycine ethyl ester in an organic solvent, adding 4-halogenated ethyl butyrate and alkali, and reacting to obtain N-benzyl glycine ethyl ester; (2) dissolving the intermediate 2 in anorganic solvent, reacting with alkali, adjusting the pH value to 7-8 after the reaction is finished, adding water for washing, adjusting the pH value of an organic layer to 1-2, and separating out crystals to obtain a crude product; and (3) dissolving the crude product in water, adding alkali to adjust the pH value to 7-8, adding an organic solvent to extract, washing, adjusting the pH value of anorganic layer to 1-2, and crystallizing to obtain the product. The method is simple in process operation, high in product yield, high in purity and easy for industrial production.
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Paragraph 0026-0029; 0043
(2020/02/10)
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- Preparation method of low-cost 3-hydroxypyridine
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The invention relates to a preparation method of low-cost 3-hydroxypyridine. The method comprises the steps of enabling 4-benzylaminobutyrate hydrochloride and 2-haloacetate to be subjected to a substitution reaction so as to obtain N-benzyl-3-aza-1, 7-pimelate diester; then, enabling the N-benzyl-3-aza-1, 7-pimelate diester to be subjected to an intramolecular condensation reaction, and carrying out hydrolytic decarboxylation to obtain N-benzylpiperidin-3-one; then, carrying out catalytic hydrogenolysis to remove benzyl so as to obtain piperidin-3-one; enabling the piperidin-3-one and halogen to be subjected to a halogenating reaction so as to obtain 2, 4-dihalogenated piperidine-3-one; then, enabling the 2, 4-dihalogenated piperidine-3-one and an acid-binding agent to be subjected to an elimination reaction to obtain 3-hydroxypyridine. The raw materials used in the preparation method are low in price and easy to obtain, the operation conditions are mild, simple and convenient, and less wastewater is produced; the method is high in operation safety, environmental protection property, product yield and purity, and low in cost.
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Paragraph 0055-0056
(2019/10/01)
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- With the biological activity of 5, 6, 7, 8 - tetrahydro-pyrido [3, 4 - d] pyrimidine compound and its preparation method and application (by machine translation)
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The invention discloses a has biological activity of 5, 6, 7, 8 - tetrahydro-pyrido [3, 4 - d] pyrimidine compound and its preparation method and application, which belongs to the with anti-tumor activity to the technical field of the synthesis of the compounds. The technical scheme of the present invention is to point: has biological activity of 5, 6, 7, 8 - tetrahydro-pyrido [3, 4 - d] pyrimidine compound, has the following structure:, wherein R1 For the ethyl carboxylic acid ester, ethylamine methyl, formyl methyl amine, dimethyl amino formyl, pyridine - 3 - methylene amino formyl, piperidine a acyl or anilino formyl, R2 For hydrogen or phenmethyl. The invention also discloses the has biological activity of 5, 6, 7, 8 - tetrahydro-pyrido [3, 4 - d] pyrimidine compound of preparation method and the preparation of anti-mammary tumor application of the medicament. The process of preparing the process is simple, easy to control, the target product high yield and good repeatability, prepared with anti-tumor activity of 5, 6, 7, 8 - tetrahydro-pyrido [3, 4 - d] pyrimidine compounds are all on breast cancer cell MCF - 7 has definite inhibitory effect. (by machine translation)
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- Preparation method for 1-benzyl-3-piperidone hydrochloride
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The invention discloses a preparation method for N-benzyl glycine ethyl ester. The method comprises the following steps: dissolving benzylamine in an organic solvent I, then adding 2-halogenated ethyl acetate, alkali and quaternary ammonium salt, and performing reaction to obtain the N-benzyl glycine ethyl ester. The invention also discloses a preparation method for 1-benzyl-3-piperidone hydrochloride. The method comprises the following specific steps: (1) preparing an intermediate IV (N-benzyl glycine ethyl ester); (2) dissolving the intermediate IV in an organic solvent II, then adding 4-halogenated ethyl acetate and alkali, and performing reaction to obtain an intermediate III; (3) performing reaction between the intermediate III and the alkali, reversely regulating a pH value to 6-8, performing concentration under reduced pressure, extracting by using ethyl acetate, performing washing and drying, and then performing concentration under reduced pressure to obtain an intermediate II; (4) performing reaction on the intermediate II and acid, performing rotary evaporation concentration, and adding a crystal solvent for crystallization to obtain a product. The route synthesis steps are short, the process is novel, the intermediates are high in purity, the product yield is high, and the cost is low.
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Paragraph 0024; 0048-0049
(2017/03/08)
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- ANTI-ANGIOGENESIS COMPOUND, INTERMEDIATE AND USE THEREOF
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Disclosed are an anti-abnormal proliferation of angiogenesis compound represented by formula I, use and intermediate thereof. The compound has good effect against abnormal proliferation of angiogenesis, and the activity of the compound is produced by inhibiting VEGFR2. The compound can be used for treating diseases, such as wet macular degeneration, inflammation, malignant tumor and the like, caused by abnormity of angiogenesis and protein kinases such as VEGFR2, FGFR2 and the like.
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- ANTI-ANGIOGENESIS COMPOUND, INTERMEDIATE AND USE THEREOF
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Disclosed are an anti-abnormal proliferation of angiogenesis compound represented by formula I, use and intermediate thereof. The compound has good effect against abnormal proliferation of angiogenesis, and the activity of the compound is produced by inhibiting VEGFR2. The compound can be used for treating diseases, such as wet macular degeneration, inflammation, malignant tumor and the like, caused by abnormity of angiogenesis and protein kinases such as VEGFR2, FGFR2 and the like.
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- Process development and scale-up of a selective α1- adrenoceptor antagonist
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A synthetic route to a potent and selective α-1-adrenergic receptor antagonist has been developed and demonstrated in a pilot plant. The route has been used in two pilot plant campaigns and has produced RO3203546 in 2.3 and 12.0 kg batch sizes. The first pilot plant campaign focused primarily on the end-game of the process with particular emphasis on the development of a method to isolate the active pharmaceutical ingredient (API). The second pilot plant campaign allowed front-end process improvements to be demonstrated. The reiterative process improvements resulted in an economical process with improved throughput and product quality when compared to the original discovery synthesis.
- Connolly, Terrence J.,Matchett, Michael,Sarma, Keshab
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- Efficient enantioselective synthesis of the NMDA 2B receptor antagonist Ro 67-8867
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An efficient, enantioselective, and scalable eight-step synthesis for the NMDA 2B receptor antagonist Ro 67-8867 (S,S)-1 selected for the treatment of acute ischemie stroke is described based on the coupling reaction of the amino alcohol (S,S)-6 with the sulfone building block 7. The synthesis of the amino alcohol (S,S)-6 was achieved by the highly selective asymmetric hydrogenation of the piperidinone 4*HCl proceeding with concomitant dynamic kinetic resolution to (S,S)-5. Subsequent debenzylation afforded the enantiomerically pure amino alcohol (S,S)-6 after ee-enhancement by simple crystallization in good yield. The hydrogenation substrate 4*HCl was prepared as a stable hydrochloride in two steps from ethyl N-benzyl-3-oxo-4-piperidinecarboxylate hydrochloride (2) for which a new, short, efficient, and cheap synthesis was developed. To bypass a mutagenic intermediate, a revised safe protocol for the sulfone building block 7 was established. The new synthesis allows the access to Ro 67-8867 (S,S)-1 in an overall yield of 53% compared to 3.5% of the Discovery Chemistry approach.
- Scalone, Michelangelo,Waldmeier, Pius
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p. 418 - 425
(2013/09/06)
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