85275-45-2Relevant academic research and scientific papers
Sustainable Route Toward N-Boc Amines: AuCl3/CuI-Catalyzed N-tert-butyloxycarbonylation of Amines at Room Temperature
Cao, Yanwei,Huang, Yang,He, Lin
, (2021/12/22)
N-tert-butoxycarbonyl (N-Boc) amines are useful intermediates in synthetic/medicinal chemistry. Traditionally, they are prepared via an indirect phosgene route with poor atom economy. Herein, a step- and atom-economic synthesis of N-Boc amines from amines, t-butanol, and CO was reported at room temperature. Notably, this N-tert-butyloxycarbonylation procedure utilized ready-made substrates, commercially available AuCl3/CuI as catalysts, and O2 from air as the sole oxidant. This catalytic system provided unique selectivity for N-Boc amines in good yields. More significantly, gram-scale preparation of medicinally important N-Boc amine intermediates was successfully implement, which demonstrated a potential application prospect in industrial syntheses. Furthermore, this approach also showed good compatibility with tertiary and other useful alcohols. Investigations of the mechanisms revealed that gold catalyzed the reaction and copper acted as electron transfer mediator in the catalytic cycle.
Multi-chiral nitrogen-substituted piperidinol derivative and preparation method thereof
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, (2021/10/11)
The invention belongs to the technical field of preparation of chiral piperidine alcohol compounds. The invention particularly relates to a multi-chiral nitrogen-substituted piperidinol derivative and a preparation method thereof. The 3 -hydroxypyridine serves as a starting raw material, and the corresponding substrate is obtained through catalytic hydrogenation reduction, amino protection, hydroxyl oxidation and Stork enamine - carbon alkylation to obtain the corresponding substrate. The process is simple, the reaction conditions are mild, and in particular, the ketone reducing liquid enzyme (KRED - 101) is selectively catalyzed, so that a chiral target product is obtained, and the yield is stable and the three wastes are few. The obtained piperidine heterocyclic derivative with the chiral center body has a plurality of drug activities and is suitable for industrial production.
PYRAZOLE DERIVATIVES AS H4 ANTAGONIST COMPOUNDS
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Paragraph 37; 46; 47, (2020/05/21)
The disclosures herein relate to novel compounds of formula (1): and salts thereof, wherein A; X;n; R1 and R2 are defined herein, and their use in treating, preventing, ameliorating, controlling or reducing the risk of disorders associated with H4 receptors.
Preparation method of (S)-N-BOC-3-hydroxypiperidine
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Paragraph 0060; 0067-0069; 0074; 0075; 0080, (2020/02/17)
The invention provides a preparation method of (S)-N-BOC-3-hydroxypiperidine. The preparation method comprises the following steps: carrying out a reaction on (S)-epichlorohydrin with a 2-chloroethylmagnesium bromide Grignard reagent to obtain (S)-1,5-dichloro-2-pentanol, carrying out an intramolecular cyclization reaction in the presence of an alkaline substance to generate (S)-5-chloro-1,2-epoxypentane, carrying out a reaction on the (S)-5-chloro-1,2-epoxypentane with an ammonia solution to generate (S)-1-amino-5-chloro-2-pentanol, then carrying out an intramolecular cyclization reaction onthe (S)-1-amino-5-chloro-2-pentanol to obtain (S)-3-hydroxypiperidine, and finally carrying out a reaction with BOC anhydride to obtain the product (S)-N-BOC-3-hydroxypiperidine. The preparation method disclosed by the invention has the advantages of short synthesis route, few side reactions and high yield; the product has good quality and is convenient for purification. The raw materials are easily available and has low price; the reaction conditions are mild; and safety is high. The preparation method is environmentally friendly, is simple and practice, and is suitable for industrial batchproduction.
Preparation method of N-tert-butyloxycarbonyl-3-piperidone and derivative thereof
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Paragraph 0065-0066; 0068-0070, (2020/07/21)
The invention discloses a preparation method of N-tert-butyloxycarbonyl-3-piperidone, and the method comprises the following step: oxidizing N-tert-butyloxycarbonyl-3-hydroxypiperidine by virtue of aNaDCC-TEMPO system so as to generate N-tert-butyloxycarbonyl-3-piperidone. The invention also discloses a method for preparing (S)-N-tert-butyloxycarbonyl-3-hydroxypiperidine through an oxidation reaction and a reduction reaction by virtue of the NaDCC-TEMPO system. The method has the advantages of simple operation steps, high conversion rate and high product purity.
A pharmaceutical intermediate N - BOC - 3 - piperidone preparation method (by machine translation)
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Paragraph 0055-0058, (2018/03/01)
The invention belongs to the field of organic synthetic technology, in particular to a pharmaceutical intermediate N - BOC - 3 - piperidone of the preparation method. To solve the problems of the prior N - BOC - 3 - piperidone in the preparation method of catalyst used is 2, 2, 6, 6 - tetramethyl piperidine nitrogen oxygen free radical or its derivatives catalytic abilities and the catalytic activity is low, the problem of catalyst is difficult to be recycled. The preparation method comprises: the 3 - hydroxy piperidine and sodium carbonate, di-T-n-butyl is the reaction in a solvent, to prepare the N - BOC - 3 - hydroxy piperidine; the N - BOC - 3 - hydroxy piperidine and potassium bromide, catalyst, sodium hypochlorite in weakly alkaline conditions arranged below the reaction in a solvent, to obtain N - BOC - 3 - piperidone. Preparation method of this invention the use of cross-linked polystyrene [...] in 9 - aza bicyclo [3, 3, 1] - nonyl - 9 - oxygen free radical as the catalyst, the use of sodium hypochlorite solution to carry out oxidation, in the method, the catalyst is easily recycled, can improve the preparation with the yield of the product, reducing N - BOC - 3 - piperidone the production cost of the, and can reduce the pollution of the environment. (by machine translation)
Stereo-complementary bioreduction of saturated N-heterocyclic ketones
Li, Chao,Liu, Yan,Pei, Xiao-Qiong,Wu, Zhong-Liu
, p. 90 - 97 (2017/04/28)
The asymmetric bioreduction of several saturated N-heterocyclic ketones is demonstrated in a stereo-complementary fashion using the ketoreductases READH and ChKRED20 for the production of (S)- and (R)-alcohols, respectively. The reaction accepts substrates with a five-, six- or seven-membered ring, and exhibits excellent stereoselectivity when using 2-propanol as both the ultimate reducing agent and cosolvent, achieve >99% ee in the majority of cases for both enantiomers.
SUBSTITUTED PYRIDINES AS INHIBITORS OF DNMT1
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Page/Page column 734, (2018/01/20)
The invention is directed to substituted pyridine derivatives. Specifically, the invention is directed to compounds according to Formula (Iar): (Iar) wherein Yar, X1ar, X2ar, R1ar, R2ar, R3ar, R4ar and R5ar are as defined herein; or a pharmaceutically acceptable salt or prodrug thereof. The compounds of the invention are selective inhibitors of DNMT1 and can be useful in the treatment of cancer, pre-cancerous syndromes, beta hemoglobinopathy disorders, sickle cell disease, sickle cell anemia, and beta thalassemia, and diseases associated with DNMT1 inhibition. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting DNMT1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
SUBSTITUTED HETEROARYL COMPOUNDS AND METHODS OF USE
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Paragraph 0400, (2017/03/28)
The present invention provides novel heteroaryl compounds, pharmaceutical acceptable salts and formulations thereof. They are useful in preventing, managing, treating or lessening the severity of a protein kinase-mediated disease. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of protein kinase-mediated disease.
Preparation method of 3-hydroxypiperidine, preparation method of derivative of 3-hydroxypiperidine, and intermediate of 3-hydroxypiperidine
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, (2017/08/27)
The invention discloses a preparation method of 3-hydroxypiperidine, a preparation method of a derivative of 3-hydroxypiperidine, and an intermediate of 3-hydroxypiperidine. The preparation method of 3-hydroxypiperidine (I) is characterized in that 5-halo-2-hydroxypentylamine halogen acid salt (III) undergoes a ring closure reaction in water under the action of an inorganic alkali to obtain the 3-hydroxypiperidine (I). The preparation method of N-protected 3-hydroxypiperidine (II) comprises the following steps: 1, 5-halo-2-hydroxypentylamine halogen acid salt (III) undergoes the ring closure reaction in water under the action of the inorganic alkali to obtain the 3-hydroxypiperidine (I); and 2, the 3-hydroxypiperidine (I) and a nitrogen protection reagent undergo an N-acylation reaction in an organic solvent under the action of the inorganic alkali to obtain the N-protected 3-hydroxypiperidine (II). The preparation methods have the advantages of simple operation, no expensive catalysts, low production cost, easily available raw materials, simplicity in operation, high reaction conversion rate, high selectivity, simple process, and suitableness for industrial production.
