- Preparation method of pitavastatin calcium intermediate
-
The invention belongs to the field of drug synthesis, and particularly relates to a preparation method of a pitavastatin calcium intermediate. The preparation method comprises the following steps: 1,carrying out a chemical reaction on a compound II and triphenylphosphine at a temperature of 10-150 DEG C to prepare a compound III; 2, in the presence of triethylamine, with oxalyl chloride and dimethyl sulfoxide as oxidants, subjecting a compound IV to a chemical reaction to prepare a compound V; and 3, subjecting the compound III and the compound V to a chemical reaction at 20-150 DEG C in thepresence of a basic catalyst so as to prepare a compound I. The intermediate prepared by using the method provided by the invention has the advantages of easy availability of raw materials, simple operation, high yield and high purity. The specific synthetic route of the method is shown in the specification.
- -
-
Paragraph 0044; 0046; 0048; 0050; 0052; 0054
(2020/02/14)
-
- Synthesis method of 2-cyclopropyl-4-(4-fluoro-phenyl)-3-quinolinecarboxaldehyde
-
The invention relates to a pharmaceutical chemical synthesis technology and in particular relates to a synthesis technology of 2-cyclopropyl-4-(4-fluoro-phenyl)-3-quinolinecarboxaldehyde. The 2-cyclopropyl-4-(4-fluoro-phenyl)-3-quinolinecarboxaldehyde is
- -
-
Paragraph 0043; 0044; 0045; 0046; 0047
(2017/02/09)
-
- Palladium-Catalyzed Carbonylative Couplings of Vinylogous Enolates: Application to Statin Structures
-
The first Pd-catalyzed carbonylative couplings of aryl and vinyl halides with vinylogous enolates are reported generating products derived from C-C bond formation exclusively at the γ-position. Good results were obtained with a dienolate derivative of acetoacetate (1,3-dioxin-4-one). These transformations occurred at room temperature and importantly with only stoichiometric carbon monoxide in a two-chamber reactor. The methodology was applied to the synthesis of two members of the statin family generating the cis-3,5-diol acid motif by a γ-selective carbonylation followed by a cis-stereoselective reduction of the 3,5-dicarbonyl acid intermediates.
- Makarov, Ilya S.,Kuwahara, Takashi,Jusseau, Xavier,Ryu, Ilhyong,Lindhardt, Anders T.,Skrydstrup, Troels
-
p. 14043 - 14046
(2015/11/25)
-
- Substrate stereocontrol in bromine-induced intermolecular cyclization: Asymmetric synthesis of pitavastatin calcium
-
A novel approach to synthesize pitavastatin calcium (1), an effective HMG-CoA reductase inhibitor, based on readily available and attractively functionalized (R)-3-chloro-1,2-propanediol is reported. This work highlights an intermolecular diastereoselective bromine-induced cyclization of homoallylic carbonate to meet stereochemical challenges in the synthesis of statins. An efficient route to a new triphenylphosphonium tetrafluoroborate salt of a quinoline core is also presented.
- Chen, Weiqi,Xiong, Fangjun,Liu, Qian,Xu, Lingjun,Wu, Yan,Chen, Fener
-
p. 4730 - 4737
(2015/07/27)
-
- PROCESS FOR THE PREPARATION OF KEY INTERMEDIATES FOR THE SYNTHESIS OF STATINS OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
-
The invention relates to commercially viable process for the synthesis of key intermediates for the preparation of statins, in particular Rosuvastatin and Pitavastatin or respective pharmaceutically acceptable salts thereof. A new simple and short synthetic route for key intermediates is presented which benefits from the use of cheap and readily available starting materials, by which the conventionally most frequently used DIBAL-H as reducing agent can be avoided.
- -
-
-
- PROCESS FOR PRODUCING QUINOLINECARBALDEHYDE
-
A novel production method of quinolinecarbaldehydes (IV), which includes reacting aminobenzophenones (I) with β-ketoaldehyde derivative (II) in the presence of an acid to give quinolinecarbaldehyde derivative (III), and then hydrolyzing the quinolinecarba
- -
-
Page/Page column 10
(2008/06/13)
-
- PROCESS FOR PREPARATION OF A QUINOLINECARBALDEHYDE
-
A process for producing 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carbaldehyde important as intermediate for the synthesis of pharmaceuticals, efficiently from an unnecessary antipode, is provided. A process for producing 2-cyclopropyl-4-(4-fluoropheny
- -
-
-
- Processes for preparing quinoline derivatives and intermedias thereof
-
The present invention provides a production method of quinoline derivative (V) wherein each symbol is as defined in the Specification, which includes reacting quinolinecarbaldehyde (I) with any of the compounds (II) to (IV) in the presence of a base, foll
- -
-
-
- Synthesis and biological evaluations of quinoline-based HMG-CoA reductase inhibitors
-
A series of quinoline-based 3,5-dihydroxyheptenoic acid derivatives were synthesized from quinolinecarboxylic acid esters by homologation, aldol condensation with ethyl acetoacetate dianion, and reduction of 3-hydroxyketone to evaluate their ability to inhibit the enzyme HMG-CoA reductase in vitro. In agreement with previous literature, a strict structural requirement exists on the external ring, and 4-fluorophenyl is the most active in this system. For the central ring, substitution on positions 6, 7, and 8 of the central quinoline nucleus moderately affected the potency, whereas the alkyl side chain on the 2-position had a more pronounced influence on activity. Among the derivatives, NK-104 (pitavastatin calcium), which has a cyclopropyl group as the alkyl side chain, showed the greatest potency. We found that further modulation and improvement in potency at inhibiting HMG-CoA reductase was obtained by having the optimal substituents flanking the desmethylmevalonic acid portion, that is, 4-fluorophenyl and cyclopropyl, instead of the usual isopropyl group.
- Suzuki,Iwasaki,Fujikawa,Kitahara,Sakashita,Sakoda
-
p. 2727 - 2743
(2007/10/03)
-
- First systematic chiral syntheses of two pairs of enantiomers with 3,5-dihydroxyheptenoic acid chain, associated with a potent synthetic statin NK-104
-
First systematic chiral syntheses of two pairs of enantiomers with 3,5-dihydroxyheptenoic acid chain, associated with a potent synthetic statin NK-104 are reported. A pair of syn diol isomers (NK-104 and its enantiomer) was obtained efficiently by diastereomeric resolution. The synthesis of a pair of anti diol isomers (3-epimer and 5-epimer) was accomplished effectively by the asymmetric aldol reaction followed by anti stereoselective reduction as key steps. Their purity determinations were effected by chiral HPLC analysis.
- Suzuki, Mikio,Yanagawa, Yoshinobu,Iwasaki, Hiroshi,Kanda, Hiroyasu,Yanagihara, Kazufumi,Matsumoto, Hiroo,Ohara, Yoshio,Yazaki, Yukari,Sakoda, Ryozo
-
p. 2977 - 2982
(2007/10/03)
-