- Synthesis method of dapoxetine impurities
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The invention provides a synthesis method of dapoxetine impurities, which comprises the following synthesis steps of: reacting (S)-3-amino-3-phenyl propanol with Boc anhydride to obtain a compound B; reducing the compound B under the action of a reducing agent to obtain a dapoxetine impurity 1; reacting the impurity 1 with 1-fluoronaphthalene under the action of alkali to obtain an impurity 2; and reacting the impurity 2 with chloroformate to obtain an impurity 3. According to the synthesis method of the dapoxetine impurities, the three dapoxetine impurities can be obtained in sequence, the starting raw materials are wide in source, the cost is low, the synthesis steps are short, all the steps are conventional experiment operation, special reagents or toxic reagents do not need to be used, and the prepared dapoxetine impurity products are high in purity and do not need tedious purification operation. The synthesized three impurities are applied to dapoxetine hydrochloride quality control, are helpful for perfecting the quality standard of dapoxetine hydrochloride, and have important meanings for improving the quality of dapoxetine hydrochloride raw material medicines and preparations thereof and the medication safety.
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Paragraph 0025; 0040-0041
(2021/07/08)
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- Synthetic method of dapoxetine and intermediate thereof
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The invention discloses a synthetic method of dapoxetine and its intermediate, i.e., (S)-3-(tert-butyloxycarbonyl)amino-3-phenylpropanol as shown in a formula 5 which is described in the specification. The synthetic method of (S)-3-(tert-butyloxycarbonyl)amino-3-phenylpropanol is as shown in a synthesis route which is described in the specification, wherein a compound 3 and acetaldehyde are subjected to a Mannich reaction in an organic solvent under the action of a supramolecular catalyst constructed by a chiral catalyst and a polymer so as to obtain a compound 4, and the polymer is at least one selected from of the group consisting of PEG 200, PEG 400, PEG 600, MeOPEG 750, PEG 800, PEG 1000, PPG 800 and PPG 1000. The dapoxetine is synthesized from the (S)-3-(tert-butyloxycarbonyl)amino-3-phenylpropanol prepared by using the above method according to steps as shown in the synthesis route. The synthetic method of dapoxetine and the intermediate thereof has the characteristics of usage of cheap and easily available raw materials, high yield and low cost, and is more beneficial to industrial production.
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Paragraph 0098-0101
(2020/03/09)
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- Chiral N,N′-Dioxide/Tm(OTf)3 Complex-Catalyzed Asymmetric Bisvinylogous Mannich Reaction of Silyl Ketene Acetal with Aldimines
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An enantioselective bisvinylogous Mannich reaction of silyl ketene acetal with aldimines has been realized by using a chiral N,N′-dioxide/Tm(OTf)3 complex as catalyst, providing an effective method to synthesize chiral ζ-amino-α,β,γ,δ-unsaturated carbonyl compounds. (Figure presented.).
- Zou, Sijia,Li, Weiwei,Fu, Kai,Cao, Weidi,Lin, Lili,Feng, Xiaoming
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supporting information
p. 2295 - 2300
(2019/04/16)
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- Configurationally Stable (S)- and (R)-α-Methylproline-Derived Ligands for the Direct Chemical Resolution of Free Unprotected β3-Amino Acids
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Reported herein is a chemical method for the direct resolution of unprotected racemic β-substituted-β-amino acids (β3-AAs) that uses specially designed, stable, and recyclable α-methylproline-derived chiral ligands. The versatility of this methodology is unmatched by biocatalytic approaches. The method shows a broad synthetic generality for various aryl- or alkyl-substituted β3-AAs, and the new nonracemizable ligands can be accessed readily. Furthermore, the presented method produces an excellent stereochemical outcome and has a fully recyclable source of chirality, and the reaction conditions are operationally simple and convenient. The procedure has also been successfully applied to the scalable synthesis of the anti-HIV drug maraviroc.
- Zhou, Shengbin,Wang, Shuni,Wang, Jiang,Nian, Yong,Peng, Panfeng,Soloshonok, Vadim A.,Liu, Hong
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p. 1821 - 1832
(2018/04/27)
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- Synthetic method for novel chiral ligand, metal chelate, multiple unnatural amino acids, maraviroc and key intermediate thereof
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The invention discloses a synthetic method for a novel chiral ligand, a metal chelate, multiple unnatural amino acids, maraviroc and a key intermediate thereof. According to the synthetic method, (R)-2-methylproline is selected as a starting material, and asymmetrical resolution is induced by utilizing a nickel chelate, so that (S)-beta3-amino acid is obtained, and (S)-3-amino-3-phenylpropionic acid is taken as the key intermediate for synthesizing maraviroc, so that yield is high, and ee value reaches more than or equal to 98.2%. The method disclosed by the invention has the advantages that source of raw materials is wide, conditions of a synthetic process are mild, control is easy, and optical purity of products is high.
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Paragraph 0501-0502
(2018/04/26)
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- Direct Asymmetric Vinylogous and Bisvinylogous Mannich-Type Reaction Catalyzed by a Copper(I) Complex
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A direct catalytic asymmetric vinylogous Mannich-type reaction has been disclosed in good yield, excellent regio-, diastereo- and enantioselectivity. The key to control the regioselectivity is the combination of a bulky N-acylpyrazole and a bulky bisphosphine ligand. The catalytic system was extended to a bisvinylogous Mannich-type reaction by changing the ligand. The synthetic utility of the vinylogous products was demonstrated by several transformations.
- Zhang, Hai-Jun,Shi, Chang-Yun,Zhong, Feng,Yin, Liang
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supporting information
p. 2196 - 2199
(2017/02/23)
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- A chiral analog of the bicyclic guanidine TBD: Synthesis, structure and Br?nsted base catalysis
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Starting from (S)-β-phenylalanine, easily accessible by lipase-catalyzed kinetic resolution, a chiral triamine was assembled by a reductive amination and finally cyclized to form the title compound 10. In the crystals of the guanidinium benzoate salt the six membered rings of 10 adopt conformations close to an envelope with the phenyl substituents in pseudo-axial positions. The unprotonated guanidine 10 catalyzes Diels-Alder reactions of anthrones and maleimides (25-30% ee). It also promotes as a strong Br?nsted base the retro-aldol reaction of some cycloadducts with kinetic resolution of the enantiomers. In three cases, the retroaldol products (48-83% ee) could be recrystallized to high enantiopurity (≥95% ee). The absolute configuration of several compounds is supported by anomalous X-ray diffraction and by chemical correlation.
- Goldberg, Mariano,Sartakov, Denis,Bats, Jan W.,Bolte, Michael,G?bel, Michael W.
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p. 1870 - 1876
(2016/10/05)
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- Process for preparation of enantiomerically pure S-(+)-N, N-dimethyl-a-[2-(naphthalenyloxy)ethyl] benzenemethanamine
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The present invention relates to improved, efficient process for the preparation of enantiomerically pure S-(+)-N,N-dimethyl-a-[2-(naphthalenyloxy)ethyl] benzenemethanamine and pharmaceutically acid addition salts thereof. The present invention particularly provides a process for preparation of (3S, 4R)-3-hydroxy-1-(4-methoxyphenyl)-4-phenylazetidin-2-one useful as a key intermediate for preparation of (s)-dapoxetine.
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- BRANCHED OXATHIAZINE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF, USE THEREOF AS MEDICINE AND DRUG CONTAINING SAID DERIVATIVES AND USE THEREOF
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The invention relates to compounds of formula (I) and to the physiologically compatible salts thereof. Said compounds are suitable, for example, for treating hyperglycemia.
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Paragraph 0359-0360
(2014/02/15)
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- Synthesis and in vitro sodium channel blocking activity evaluation of novel homochiral mexiletine analogs
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New chiral mexiletine analogs were synthesized in their optically active forms and evaluated in vitro as use-dependent blockers of skeletal muscle sodium channels. Tests carried out on sodium currents of single muscle fibers of Rana esculenta demonstrated
- Carocci, Alessia,Catalano, Alessia,Bruno, Claudio,Lentini, Giovanni,Franchini, Carlo,De Bellis, Michela,De Luca, Annamaria,Camerino, Diana Conte
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experimental part
p. 299 - 307
(2010/10/21)
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- A designer axially chiral amino sulfonamide as an efficient organocatalyst for direct asymmetric mannich reactions of N-boc-protected imines
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The moderate nucleophilicity of the axially chiral amino sulfonamide (S)-1 suppresses the problematic side reactions, including aldol reactions, in the asymmetric Mannich reaction of N-Boc-protected imines with aldehydes. The corresponding adducts are obtained in good yield and excellent stereoselectivity (see scheme; Boc=tert-butoxycarbonyl, Tf=trifluoromethanesulfonyl).
- Kano, Taichi,Yamaguchi, Yukako,Maruoka, Keiji
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supporting information; experimental part
p. 1838 - 1840
(2009/08/14)
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- An efficient formal synthesis of (S)-dapoxetine from enantiopure 3-hydroxy azetidin-2-one
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An efficient formal synthesis of S-(+) dapoxetine starting from 3-hydroxy azetidin-2-one is described. The intermediate (S)-3-(dimethyl amino)-3-phenylpropan-1-ol was synthesized in enantiopure form starting with 3-hydroxy azetidin-2-one in seven steps.
- Chincholkar, Pinak M.,Kale, Ajaykumar S.,Gumaste, Vikas K.,Deshmukh, Abdul Rakeeb A.S.
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experimental part
p. 2605 - 2609
(2009/08/08)
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- Direct organocatalytic Mannich reaction of acetaldehyde: An improved catalyst and mechanistic insight from a computational study
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(Chemical Equation Presented) A chiral diaryl prolinol silyl ether organocatalyst with an acidis used for the direct catalytic asymmetric Mannich reaction of acetaldehyde and imines. N-Benzoyl-, N-tert-butoxycarbonyl-, and N-toluene-4-sulfonylimines can be employed to produce synthetically useful β-amino aldehydes in goodyield s andwith excellent enantioselectivity (see scheme). The reaction mechanism was investigated quantum-mechanically.
- Hayashi, Yujiro,Okano, Tsubasa,Itoh, Takahiko,Urushima, Tatsuya,Ishikawa, Hayato,Uchimaru, Tadafumi
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supporting information; experimental part
p. 9053 - 9058
(2009/02/08)
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- Enantioselective synthesis of (S)-dapoxetine
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An efficient enantioselective synthesis leading directly to (+)-(S)-dapoxetine has been described for the first time using a Sharpless asymmetric dihydroxylation, Barton-McCombie deoxygention, and Mitsunobu reaction as the key steps.
- Siddiqui, Shafi A.,Srinivasan, Kumar V.
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p. 2099 - 2103
(2008/02/11)
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- Chiral Bronsted acid-catalyzed tandem aza-ene type reaction/cyclization cascade for a one-pot entry to enantioenriched piperidines
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A chiral monophosphoric acid-catalyzed tandem aza-ene type reaction/cyclization cascade enabled the rapid construction of enantioenriched piperidine derivatives as key structural elements of numerous natural products. The potential of such cascade transformations is highlighted through their ability to achieve a rapid increase in molecular complexity from simple enecarbamates and a broad range of aldimines while also controlling three stereogenic centers in a highly diastereo- and enantioselective manner. Copyright
- Terada, Masahiro,Machioka, Kyoko,Sorimachi, Keiichi
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p. 10336 - 10337
(2008/03/13)
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- Iridium(I)-catalyzed regio- and enantioselective allylic amidation
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Ir(I)-catalyzed intermolecular allylic amidation of ethyl allyl carbonates with soft nitrogen nucleophiles under completely 'salt-free' conditions is described. A combination of [Ir(COD)Cl]2, a chiral phosphoramidite ligand L*, and DBU as a base in THF effects the reaction. The reaction appears to be quite general, accommodating a wide variety of R-groups and soft nitrogen nucleophiles, and proceeds with excellent regio- and enantioselectivities to afford the branched N-protected allylic amines. The developed reaction was conveniently utilized in the asymmetric synthesis of N-Boc protected α- and β-amino acids as well as (-)-cytoxazone.
- Singh, Om V.,Han, Hyunsoo
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p. 7094 - 7098
(2008/03/11)
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- PIPERIDINE DERIVATIVES AS CCR5 RECEPTOR MODULATORS
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Compounds of formula (I) wherein R1, R2, R3, A and n are as defined; and X is S(O)2 NR4R5 or NR6S(O)2R7; compositions comprising them, processes for preparing them and their use in medical therapy (for example modulating CCR5 receptor activity in a warm blooded animal).
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Page/Page column 51-52
(2010/02/10)
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- NOVEL PIPERIDINE DERIVATIVES AS MODULATORS OF CHEMOKINE RECEPTOR CCR5
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Compounds of formula (I) wherein R1, R2, R3, R4, A, X, m and n are as defined; compositions comprising them, processes for preparing them and their use in medical therapy (for example modulating CCR5 receptor activity in a warm blooded animal).
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Page 92 - 93
(2010/02/07)
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- (1′S,4S)-2-Aryl-4-(1′-hydroxybenzyl)-4,5-dihydro-oxazole as a useful chiral auxiliary for the synthesis of β-amino acids and β-lactams in a highly stereoselective manner
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(1′5,45)-2-Aryl-4-(1′-hydroxybenzyl)-4,5-dihydrooxazole prepared from (1S,2S)-2-amino-l-phenylpropane-l,3-diol has been found to be a useful chiral auxiliary for the stereoselective synthesis of β-lactams and β-amino acids in the reaction of imine-ester enolate condensation or 1,4-addition of lithium amides to α,β-unsaturated esters.
- Shimizu, Makoto,Maruyama, Shingo,Suzuki, Yasuhiro,Fujisawa, Tamotsu
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p. 1883 - 1889
(2007/10/03)
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- A Concise Enantioselective Synthesis of Allylamines and N-Boc-β-Amino Acids
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A new and efficient enantioselective synthesis of allylamines and N-Boc-β-amino acids has been developed.Starting from enantiomerically enriched N-diphenylmethyl-3-amino-1,2-diols, allylamines are easily obtained by a Corey-Hopkins deoxygenative protocol.After a change in the nitrogen protecting group, the resulting N-Boc allylamines are converted into β-amino acids by hydroboration with 9-BBN followed by oxidation with PDC in DMF.
- Alcon, Montserrat,Canas, Marc,Poch, Marta,Moyano, Albert,Pericas, Miquel A.,Riera, Antoni
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p. 1589 - 1592
(2007/10/02)
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