- Manganese-Mediated Direct Functionalization of Hantzsch Esters with Alkyl Iodides via an Aromatization-Dearomatization Strategy
-
We report, for the first time, manganese-mediated direct functionalization of the Hantzsch esters with readily accessible alkyl iodides through an aromatization-dearomatization strategy. Applying this protocol, a library of valuable 4-alkyl-1,4-dihydropyridines were facilely afforded in good yields. This simple and practical reaction proceeds under visible-light irradiation at room temperature and displays high functional-group compatibility. Additionally, the method is applicable for gram-scale synthesis and late-stage functionalization of complex molecules.
- Liu, Xian-Guan,Dong, Ci-Shuang,Li, Fei,Zhang, Bo
-
supporting information
p. 4002 - 4007
(2021/05/26)
-
- Quinim: A New Ligand Scaffold Enables Nickel-Catalyzed Enantioselective Synthesis of α-Alkylated ?-Lactam
-
Herein, we report a nickel-catalyzed reductive cross-coupling reaction of easily accessible 3-butenyl carbamoyl chloride with primary alkyl iodide to access the chiral α-alkylated pyrrolidinone with broad substrate scope and high enantiomeric excess. The current art of synthesis still remains challenging on the enantioselective α-monoalkylation of pyrrolidinones. The newly designed chiral 8-quinoline imidazoline ligand (Quinim) is crucial for maintaining the reactivity and enantioselectivity to ensure the reductive cyclization of monosubstituted alkenes for unprecedented synthesis of chiral non-aromatic heterocycles.
- Chen, Yifeng,Qu, Jingping,Wu, Xianqing
-
supporting information
p. 15654 - 15660
(2020/10/18)
-
- Preparation method of 1-chloro-6-iodohexane
-
The invention discloses a preparation method of 1-chloro-6-iodohexane. The preparation method comprises the steps of with 6-chloro-1-hexanol and p-toluene sulfochloride as the materials and benzene ortoluene as a solvent, reacting at (-5)-(5) DEG C for 2-5 hours under the effects of a phase transfer catalyst and an acid-binding agent so as to prepare 4-methylbenzenesulfonic acid-6-chlorohexyl ester, and carrying out reflux reaction on 4-methylbenzenesulfonic acid-6-chlorohexyl ester and sodium iodide for 0.5-3 hours, so as to prepare 1-chloro-6-iodohexane. The preparation method has the characteristics of easiness in operation, simplicity and convenience in after-treatment and relatively high yield.
- -
-
Paragraph 0011-0014
(2019/04/09)
-
- OXALATE SALTS OF TENELIGLIPTIN AND SOLVATES THEREOF, INTERMEDIATES, PROCESS OF PREPARATION
-
The present invention provides oxalate salts of teneligliptin and solvates thereof exhibiting superior physiochemical properties. In particular, crystalline form of teneligliptin 2.5 oxalate 1.0 hydrate and crystalline form of teneligliptin 3.0 oxalate 1.0 hydrate are disclosed. Also provided are methods of preparing the same, and uses thereof.
- -
-
Paragraph 00186
(2018/08/26)
-
- Method for preparing hydrobromic acid teneligliptin
-
The invention provides a method for preparing hydrobromic acid teneligliptin. The method includes steps of preparing L-hydroxyproline; mixing the L-hydroxyproline and sodium bicarbonate with each other to obtain mixtures, dissolving the mixtures in water, adding acetone into the water, dropping di-tert-butyl dicarbonate into the water, carrying out room-temperature reaction overnight and then treating reaction products to obtain t-butyloxycarboryl-N-hydroxyproline; preparing t-butyloxycarboryl-N-4-oxo-proline from the t-butyloxycarboryl-N-hydroxyproline; preparing (2S)-4-oxo-2-(3-thiazolidine carbonyl)-1-pyrrolidine carboxylic acid tert-butyl ester from the t-butyloxycarboryl-N-4-oxo-proline; preparing compounds III from compounds IV; preparing compounds II from the compounds III; preparing compounds 1-(3-methyl-1-phenyl-1H-pyrazole-5-base) piperazine from the compounds II; preparing intermediates I; preparing the hydrobromic acid teneligliptin from the intermediates I. The method has the advantages that the method is low in cost, and the cost of the method is only two-thirds of the cost of an existing method in the prior art; the yield of the hydrobromic acid teneligliptin is higher than 95%, and the purity of the hydrobromic acid teneligliptin is higher than 98%.
- -
-
Paragraph 0043; 0044; 0059
(2017/07/01)
-
- Process for the preparation of teneligliptin
-
A process for the preparation of teneligliptin.
- -
-
-
- Discovery and preclinical profile of teneligliptin (3-[(2S,4S)-4-[4-(3- methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl] thiazolidine): A highly potent, selective, long-lasting and orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
-
Dipeptidyl peptidase IV (DPP-4) inhibition is suitable mechanism for once daily oral dosing regimen because of its low risk of hypoglycemia. We explored linked bicyclic heteroarylpiperazines substituted at the γ-position of the proline structure in the course of the investigation of l-prolylthiazolidines. The efforts led to the discovery of a highly potent, selective, long-lasting and orally active DPP-4 inhibitor, 3-[(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5- yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl]thiazolidine (8g), which has a unique structure characterized by five consecutive rings. An X-ray co-crystal structure of 8g in DPP-4 demonstrated that the key interaction between the phenyl ring on the pyrazole and the S2 extensive subsite of DPP-4 not only boosted potency, but also increased selectivity. Compound 8g, at 0.03 mg/kg or higher doses, significantly inhibited the increase of plasma glucose levels after an oral glucose load in Zucker fatty rats. Compound 8g (teneligliptin) has been approved for the treatment of type 2 diabetes in Japan.
- Yoshida, Tomohiro,Akahoshi, Fumihiko,Sakashita, Hiroshi,Kitajima, Hiroshi,Nakamura, Mitsuharu,Sonda, Shuji,Takeuchi, Masahiro,Tanaka, Yoshihito,Ueda, Naoko,Sekiguchi, Sumie,Ishige, Takayuki,Shima, Kyoko,Nabeno, Mika,Abe, Yuji,Anabuki, Jun,Soejima, Aki,Yoshida, Kumiko,Takashina, Yoko,Ishii, Shinichi,Kiuchi, Satoko,Fukuda, Sayaka,Tsutsumiuchi, Reiko,Kosaka, Keigo,Murozono, Takahiro,Nakamaru, Yoshinobu,Utsumi, Hiroyuki,Masutomi, Naoya,Kishida, Hiroyuki,Miyaguchi, Ikuko,Hayashi, Yoshiharu
-
p. 5705 - 5719
(2012/10/30)
-
- Pheromone synthesis. Part 244: Synthesis of the racemate and enantiomers of (11Z,19Z)-CH503 (3-acetoxy-11,19-octacosadien-1-ol), a new sex pheromone of male Drosophila melanogaster to show its (S)-isomer and racemate as bioactive
-
The enantiomers of (11Z,19Z)-3-acetoxy-11,19-octacosadien-1-ol were synthesized from the enantiomers of 3,4-epoxy-1-butanol PMB ether. Its racemate was also synthesized. Its (S)-isomer and racemate were shown to possess the same pheromone activity as CH503, a long-lived inhibitor of male courtship in Drosophila melanogaster, although the racemate was less active.
- Mori, Kenji,Shikichi, Yasumasa,Shankar, Shruti,Yew, Joanne Y.
-
experimental part
p. 7161 - 7168
(2010/10/01)
-
- CONCOMITANT PHARMACEUTICAL AGENTS AND USE THEREOF
-
A concomitant agent to be used simultaneously or separately, comprising a combination of (a) 3-{(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl}thiazolidine, a salt of the compound with an organic or inorganic and mono- or di-basic acid or a solvate thereof, and (b) at least one kind of active ingredient selected from the group consisting of an active ingredient of a pharmaceutical agent selected from (i) an antidiabetic drug, (ii) a lipid lowering drug, (iii) an antihypertensive drug, (iv) a therapeutic drug for diabetic complications, (v) an antiobesity drug, (vi) an antiplatelet drug and (vii) an anticoagulant, a pharmaceutically acceptable salt thereof and a solvate thereof.
- -
-
Page/Page column 12
(2008/06/13)
-
- SALT OF PROLINE DERIVATIVE, SOLVATE THEREOF, AND PRODUCTION METHOD THEREOF
-
The present invention provides 3-{(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl}thiazolidine (compound I) useful as a dipeptidyl peptidase-IV inhibitor, which has superior properties of stability and hygroscopicity, and reproducible crystal structure, and a production method thereof.
- -
-
Page/Page column 8
(2008/06/13)
-
- A new direct homolytic iodination reaction of alkanes by perfluoroalkyl iodides
-
A new method for the direct free-radical chain iodination of alkanes by perfluoroalkyl iodides is described.
- Liguori, Lucia,Bjorsvik, Hans-Rene,Bravo, Anna,Fontana, Francesca,Minisci, Francesco
-
p. 1501 - 1502
(2007/10/03)
-
- LONG-ACTING CONTRACEPTIVE AGENTS: ESTERS OF NORETHISTERONE WITH ALKOXY- AND HALOGENO-SUBSTITUTED CARBOXYLIC ACIDS
-
The chemical synthesis and physical data of several new esters of norethisterone (17α-ethynyl-17β-hydroxyestr-4-en-3-one) are reported, which contain either a chloro- or an alkoxy-group as a substituent in the acid side-chain.
- Shafiee, A.,Vossoghi, M.,Francisco, C. G.,Freire, R.,Hernandez, R.,et al.
-
p. 285 - 290
(2007/10/02)
-
