266353-18-8

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 623-33-6 glycine ethyl ester hydrochloride 
• 107-13-1 acrylonitrile 
• 3088-42-4 N-(2-cyanoethyl)glycine 
• 44981-94-4 N-cyanoethyl glycine ethyl ester 

Downstream Products

• 175463-32-8 3-cyano-4-oxopyrrolidine-1-carboxylic acid tert-butyl ester 
• 773826-73-6 tert-butyl 3-(aminomethyl)-4-hydroxypyrrolidine-1-carboxylate 
• 197143-33-2 tert-butyl 3-cyano-4-hydroxypyrrolidine-1-carboxylate 
• 175463-34-0 4-(tert-butoxycarbonyl)aminomethyl-1-(t-butoxycarbonyl)pyrrolidin-3-ol 
• 175463-14-6 gemifloxacin 
• 827318-78-5 5-((R)-2-methoxy-2-phenylacetyl)-3-[4-(4-methylpiperazin-1-yl)benzoylamino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid ethyl ester 
• 916995-51-2 danusertib 
• 398495-65-3 3-amino-4,6-dihydro-pyrrolo[3,4-c]pyrazole-1,5-dicarboxylic acid 5-tert-butyl ester 1-ethyl ester 
• 761443-69-0 5-tert-butyl 1-ethyl 3-{[4-(4-methylpiperazin-1-yl)benzoyl]amino}-4,6-dihydropyrrolo[3,4-c]pyrazole-1,5-dicarboxylate 
• 761443-50-9 3-[4-(N-methylpiperazin-1-yl)benzamido]-1-ethoxycarbonyl-4,6-dihydropyrrolo[3,4-c]pyrazole 
• 398491-59-3 3-amino-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carboxylic acid tert-butyl ester 
• 1312572-60-3 4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-diazepan-2-one 
• 1312572-57-8 4-[5-(3-methyl-5-{[4-(methylsulfinyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-diazepan-2-one 
• 1312572-56-7 4-{5-[3-({4-[(2-hydroxyethyl)sulfanyl]pyrimidin-2-yl}amino)-5-methylphenyl]-1,3-thiazol-2-yl}-1,4-diazepan-2-one 

Relevant academic research and scientific papers

A preparation method of the lucky mischa star side chain

The invention relates to a preparation method of a gemifloxacin side chain. The preparation method comprises that N-tertbutyloxycarbonyl-4-cyano-3-pyrrolidone is prepared or taken and then reacts with trimethyl orthoformate to produce N-tertbutyloxycarbonyl-4-cyano-3-dimethoxypyrrolidone, the N-tertbutyloxycarbonyl-4-cyano-3-dimethoxypyrrolidone, methanol, a catalyst and (BOC)2 anhydride undergo a complete reaction at a room temperature to produce N-tertbutyloxycarbonyl-4-aminomethyl-3-dimethoxypyrrolidone, the N-tertbutyloxycarbonyl-4-aminomethyl-3-dimethoxypyrrolidone and HAC undergo a complete reaction at a room temperature with stirring to produce N-tertbutyloxycarbonyl-4-aminomethyl-3-pyrrolidone, and the N-tertbutyloxycarbonyl-4-aminomethyl-3-pyrrolidone is transformed into the gemifloxacin side chain 4-aminomethyl-3-methoxyiminopyrrolidone. The preparation method has simple processes, allows mild reaction conditions easily to be realized, has a low raw material price, a low cost and less environmental pollution and creates a novel gemifloxacin side chain pyrrolidone ketonic group protection method and a gemifloxacin side chain synthesis route.

Preparation method of zabofloxacin intermediate

The invention provides a preparation method of a zabofloxacin intermediate. The method comprises: reacting ethyl glycinate hydrochloride with acrylonitrile under catalysis of a base to form an intermediate I; then reacting the intermediate I with Boc anhydride under the function of a strong base to generate an intermediate III; reacting the intermediate III, the methoxyamine hydrochloride and formaldehyde to generate an intermediate IV; and then preparing the zabofloxacin intermediate by reacting the intermediate IV with methanesulfonyl chloride, performing reduction with sodium borohydride, and other steps. The zabofloxacin intermediate is prepared through nine steps with a high yield and high quality by the method, the material adding amount reaches the level of hundreds of grams, and the method is suitable for industrial production.

(R)- N - [5 - (2 - methoxy - 2 - phenyl-acetyl) - 1, 4, 5, 6 - tetrahydro-pyrrolo [3, 4 - c] pyrazole - 3 - yl] - 4 - (4 - methyl piperazine - 1 - yl) benzamide synthesis method

The invention belongs to the technical field of medicine and relates to a preparation method for PHA739358(Danusertib), i.e., (R)-N-[5-(2-methoxy-2-phenylacetyl)-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole-3-yl]-4-(4-methyl piperazine-1-yl)benzamide. According to the invention, altogether four reaction routes are designed, simple and easily available glycine is used as a raw material, reactions like addition, esterification, amino protection and cyclization are carried out so as to prepare (R)-N-[5-(2-methoxy-2-phenylacetyl)-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole-3-yl]-4-(4-methyl piperazine-1-yl)benzamide, yield of the route 1, 2 and 4 is more than 25%, respectively, and yield of the route 3 is more than 20%. The preparation method has the advantages of a few reaction steps, simple and convenient post-treatment operation, little time consumption, high yield and low total cost. Thus, a novel method is provided for preparation of the antitumor drug PHA739358.

Gemifloxacin intermediate preparation method

The invention relates to medicine and related fields, and especially relates to a gemifloxacin intermediate preparation method. According to the invention, acrylonitrile and ethyl glycinate hydrochloride are adopted as initial raw materials; through the processes of a nucleophilic addition reaction, amino protection, condensation, reduction protection, oxidation, oximation and deprotection, the gemifloxacin branched-chain intermediate 4-aminomethylpyrrolidin-3-one-O-methyloxime dihydrochloride is obtained. The route is simple; two steps of reactions are eliminated; raw materials are cheap and easy to obtain; and product yield is high. The route does not need column chromatography separation. The method provides a feasible synthesis route for industrial production.

Synthesis and in-vitro antibacterial activity of 7-(3-aminopyrrolo[3,4-c] pyrazol-5(2H,4H,6H)-yl)-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid derivatives

A series of novel 7-(3-aminopyrrolo[3,4-c]pyrazol-5(2H,4H,6H)-yl)-6-fluoro- 4-oxo-1,4-dihydroquinoline-3-carboxylic acid derivatives was designed, synthesized and characterized by 1H-NMR, MS and HRMS. These fluoroquinolones were evaluated for their in-vitro antibacterial activity against representative Gram-positive and Gram-negative strains. Generally, all of the target compounds display rather weak potency against the tested Gram-negative strains, but most of them exhibit good potency in inhibiting the growth of S. aureus including methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis including methicillin-resistant S. epidermidis (MRSE) (MIC: 0.125-8 μg/mL). In particular, the compound 9g is 2 to 32 fold more potent than gemifloxacin (GM), moxifloxacin (MX), gatifloxacin (GT), and levofloxacin (LV) against S. pneumoniae 08-3, K. pneumoniae 09-23, and P. aeruginosa ATCC27853, 4 to 32 fold more potent than MX, GM, and LV against K. pneumoniae 09-21, and more active than or comparable to the four reference drugs against P. aeruginosa 09-32. A series of novel fluoroquinolone derivatives was designed and synthesized. All target compounds display rather weak potency against the tested Gram-negative strains, but most of them exhibit good potency in inhibiting the growth of Staphylococcus aureus and Staphylococcus epidermidis. In particular, the compound 9g is the most promising drug.

AMINOPYRIMIDINES AS SYK INHIBITORS

The present invention provides novel pyrimidine amines of formula (I) which are potent inhibitors of spleen tyrosine kinase, and are useful in the treatment and prevention of diseases mediated by said enzyme, such as asthma, COPD and rheumatoid arthritis.

Synthesis and in vitro antibacterial activity of fluoroquinolone derivatives containing 3-(N′-alkoxycarbamimidoyl)-4-(alkoxyimino) pyrrolidines

A series of novel 7-[3-(N′-alkoxycarbamimidoyl)-4-(alkoxyimino) pyrrolidin-1-yl] fluoroquinolone derivatives were designed, synthesized and characterized by 1H NMR, MS and HRMS. These fluoroquinolones were screened for their in vitro antibacter

Synthesis and biological activity of novel 1β-Methylcarbapenems with oxyiminopyrrolidinylamide moiety

The synthesis and antibacterial activity of novel 1β- methylcarbapenems 1a-f bearing oxyiminopyrrolidinylamide moiety at C-5 position of pyrrolidine are described. Most compounds exhibited comparable antibacterial activity to meropenem against a wide range of Gram-positive and Gram-negative organisms including Pseudomonas aeruginosa isolates. Of these carbapenems, 1a showed potent and broad spectrum of antibacterial activity and similar stability to DHP-I to meropenem. Against clinical isolates of 40 Gram-negative bacterial species including MDR and ESBL-producing strains, the selected carbapenem 1a possessed excellent in vitro activity except for MDR P. aeruginosa, and was comparable in potency to meropenem.

Process for producing an N-alkoxycarbonyl-N-cyanoethyl amino acid alkyl ester

An N-alkoxycarbonyl-N-cyanoethyl amino acid alkyl ester is produced at a high yield by reacting a mineral acid salt of amino acid alkyl ester with acrylonitrile in an alcohol medium in the presence of an inorganic base to form an N-cyanoethyl amino acid alkyl ester and then reacting the N-cyanoethyl amino acid alkyl ester with a dialkyl dicarbonate.

Novel fluoroquinolone antibacterial agents containing oxime-substituted (Aminomethyl)pyrrolidines: Synthesis and antibacterial activity of 7-(4- (Aminomethyl)-3-(methoxyimino) pyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4- oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylic acid (LB20304)

New pyrrolidine derivatives, which bear an alkyloxime substituent in the 4-position and an aminomethyl substituent in the 3-position of the pyrrolidine ring, have been synthesized and coupled with various quinolinecarboxylic acids to produce a series of new fluoroquinolone antibacterials. These fluoroquinolones were found to possess potent antimicrobial activity against both Gram-negative and Gram-positive organisms, including methicillin resistant Staphylococcus aureus (MRSA). Variations at the C-8 position of the quinolone nucleus included fluorine, chlorine, nitrogen, methoxy, and hydrogen atom substitution. The activity imparted to the substituted quinolone nucleus by the C-8 substituent was in the order F (C5-NH2) > F (C5-H) > naphthyridine > Cl = OMe = H against Gram-positive organisms. In the case of Gram-negative strains, activity was in the order F (C5-NH2) > naphthyridine = F (C5-H) > H > Cl > OMe. The advantages provided by the newly introduced oxime group of the quinolones were clearly demonstrated by their comparison to a desoximino compound 30. In addition, the oxime moiety greatly improved the pharmacokinetic parameters of the novel quinolones. Among these compounds, compound 20 (LB20304) showed the best in vive efficacy and pharmacokinetic profile in animals, as well as good physical properties. The MICs (μg/mL) of LB20304, compound 30, and ciprofloxacin against several test organisms are as follows: S. aureus 6538p (0.008, 0.031, and 0.13), methicillin resistant S. aureus 241 (4, 16, and 128), Streptococcus epidermidis 887E (0.008, 0.016, and 0.13), methicillin resistant S. epidermidis 178 (4, 32, and 128), Enterococcus faecalis 29212 (0.063, 0.13, and 1), Pseudomonas aeruginosa 1912E (0.25, 0.5, and 0.13), Escherichia coli 3190Y (0.008, 0.016, and 0.008), Enterobacter cloacae P99 (0.008, 0.031, and 0.008), Actinobacter calcoaceticus 15473 (0.063, 0.13, and 0.25). On the basis of these promising results, LB20304 was selected as a candidate for further evaluation.