- Nickel-Catalyzed Intramolecular Hydroalkenylation of Imines
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A ligand-enabled nickel-catalyzed intramolecular hydroalkenylation of imines with unactivated alkenes has been developed. A variety of five- and six-membered cyclic allylic amines were synthesized in high yields. The use of both wide-bite-angle diphosphine ligand and Br?nsted acid is crucial for realizing the reaction. Preliminary investigation of the asymmetric intramolecular hydroalkenylation of imines shows promising potential for the application of the method in the synthesis of enantio-enriched cyclic allylic amines.
- Feng, Wei-Min,Li, Tian-Yu,Xiao, Li-Jun,Zhou, Qi-Lin
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supporting information
p. 7900 - 7904
(2021/10/12)
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- TBuO 2H/Cu(acac) 2-Mediated Intramolecular Oxidative Lactonization of o -Allyl Arylaldehydes: Synthesis of 1-Oxoisochromans
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A concise route for the tBuO 2H/Cu(acac) 2-mediated synthesis of 1-oxoisochromans is described. This includes: (i) oxidation of oxygenated o -allyl arylaldehydes and (ii) sequential intramolecular lactonization of the resulting olefin-containing benzoic acids. A plausible mechanism is proposed and discussed.
- Chang, Meng-Yang,Lai, Kai-Xiang,Chen, Kuan-Ting
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p. 527 - 537
(2020/10/19)
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- PdCl2/CuCl2/Bi(OTf)3-promoted Construction of Sulfonyl Dibenzooxabicyclo[3.3.1]nonanes and Arylnaphthalenes via Intramolecular Annulation of Sulfonyl o-Allylarylchromanones
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PdCl2/CuCl2/Bi(OTf)3-promoted intramolecular domino annulation of sulfonyl o-allylarylchromanones provides tetracyclic sulfonyl dibenzooxabicyclo[3.3.1]nonanes and bicyclic arylnaphthalenes with good to excellent yields in MeOH at room (25 °C) and refluxing (65 °C) temperature, respectively. The starting sulfonyl o-allylarylchromanones can be easily obtained from the intermolecular cyclocondensation of α-sulfonyl o-hydroxyacetophenones and o-allylbenzaldehydes. The uses of various catalysts and solvent systems are investigated herein for convenient transformation. A plausible mechanism is proposed and discussed. This protocol provides one-pot ring closure via carbon-carbon (C?C) bond formation. (Figure presented.).
- Chang, Meng-Yang,Hsueh, Nai-Chen
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supporting information
p. 5736 - 5750
(2020/12/01)
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- Synthesis of 3-Azidopiperidine Skeleton Employing Ceric Ammonium Nitrate (CAN)-Mediated Regioselective Azidoalkoxylation of Enol Ether: Total Synthesis of D2 Receptor Agonist (±)-Quinagolide
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The total synthesis of (±)-quinagolide, which is a D2 receptor agonist, was accomplished via a ceric ammonium nitrate (CAN)-mediated regioselective azidoalkoxylation of enol ether route. Key features of the synthesis include Claisen rearrangement, PPTS (pyridinium p-toluenesulfonate)-catalyzed one-pot acetal deprotection, followed by a diastereoselective Henry reaction, which enables construction of the required trans ring junction and CAN-mediated regioselective azidoalkoxylation of enol ether. The PPTS-catalyzed intramolecular diastereoselective Henry reaction to fix three contiguous stereocenters on tetrahydronaphthalene and the first-of-its-kind synthesis of the 3-azidopiperidine skeleton, using a CAN-mediated regioselective azidoalkoxylation of enol ether, are important findings of the present work.
- Chavan, Subhash P.,Kadam, Appasaheb L.,Lasonkar, Pradeep B.,Gonnade, Rajesh G.
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supporting information
p. 7011 - 7014
(2018/11/23)
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- Synthesis of Polysubstituted 3-Methylisoquinolines through the 6π-Electron Cyclization/Elimination of 1-Azatrienes derived from 1,1-Dimethylhydrazine
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A convenient one pot microwave-assisted 6π-electron cyclization/aromatization approach toward 3-methylisoquinolines is reported. The starting 1-azatriene derivatives were prepared in situ by reaction of 2-propenylbenzaldehydes with 1,1-dimethylhydrazine, which exhibited superior performance when compared with other hydrazine derivatives. Minor amounts of the related 3,4-dihydro isoquinolines were formed concomitantly with the isoquinolines, and a mechanism for their generation was proposed. The reaction conditions were optimized, and its scope and limitations were explored. In general, the transformation proceeded in moderate to good yields.
- Vargas, Didier F.,Larghi, Enrique L.,Kaufman, Teodoro S.
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p. 5605 - 5614
(2018/10/09)
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- PROCESS FOR PREPARATION OF PROSTACYCLIN DERIVATIVES
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Disclosed is an improved method of synthesis for Treprostinil comprising condensation reaction of compound (4) with a hydroxyl-protected alkynol (5) to give the condensation product, compound (6). Subjecting compound (6) to oxidation, reduction, hydroxyl protection and carbonylation, cyclization reactions gives the tricyclic derivative (10). Further reactions comprising reduction, hydrogenation and deprotection of the phenolic and side-chain hydroxyl groups, wherein the sequence and choice of reagents is governed by protecting groups, give the triol intermediate, compound (14). Cyanoalkylation at phenolic hydroxyl functionality and further hydrolysis yields the prostacyclin compound, Treprostinil (1) and its pharmaceutically acceptable salts with desired purity.
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Page/Page column 26
(2017/08/21)
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- CuI Mediated One-Pot Cycloacetalization/Ketalization of o-Carbonyl Allylbenzenes: Synthesis of Benzobicyclo[3.2.1]octane Core
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CuI/DMSO-mediated intramolecular cycloacetalization/ketalization of o-carbonyl allylbenzenes has been achieved for constructing [6,6,5]-tricycles having a ketal motif in good yields. The expeditious one-step route provides a three C-O bond formation. The key products with the structural framework of a benzofused dioxabicyclo[3.2.1]octane core have been confirmed by X-ray crystallographic analysis. Synthesis of dihydroisocoumarin has been studied.
- Chan, Chieh-Kai,Tsai, Yu-Lin,Chang, Meng-Yang
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p. 1870 - 1873
(2017/04/11)
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- AMINE SALTS OF A PROSTACYCLIN ANALOG
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The present invention provides amine salts of the prostacyclin analogue of Formula I and processes for generating these amine salts.
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- METHODS OF SYNTHESIZING A PROSTACYCLIN ANALOG
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The present invention provides processes for preparing a prostacyclin analogue of Formula (I) or a pharmaceutically acceptable salt thereof, wherein R10 is a linear or branched C1-6 alkyl. The processes of the present invention comprise steps that generate improved yields and fewer byproducts than traditional methods. The processes of the present invention employ reagents (e.g., the oxidizing reagent) that are less toxic that those used in the traditional methods (e.g., oxalyl chloride). Many of the processes of the present invention generate intermediates with improved e.e. and chemical purity; thereby eliminating the need of additional chromatography steps. And, the processes of the present invention are scalable to generate commercial quantities of the final compound.
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- One-pot access to 2-naphthols and benzofurans via the aerobic Wacker-type oxidation/intramolecular aldol cyclization
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An aerobic Wacker-type oxidation/intramolecular aldol cyclization synthetic route toward two oxygenated 2-naphthols 3 and benzofurans 4 starting with skeleton 2 with good yields is described. The route has been carried by the one-pot transformation of the regioselective PdCl2/CuCl 2-mediated Wacker oxidative cyclization of skeleton 2 with molecular oxygen under the alkaline methanolic condition. Skeleton 2 was prepared from skeleton 1 in moderate total yields via the known protocol.
- Chang, Meng-Yang,Chan, Chieh-Kai,Lin, Shin-Ying
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p. 1532 - 1538
(2013/02/25)
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- SYNTHESIS OF INTERMEDIATE FOR TREPROSTINIL PRODUCTION
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The compound according to Formula I is an intermediate in the synthesis of prostacylin analogs. The present invention provides an efficient method for synthesizing a Formula I compound.
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- Synthesis of dihydrobenzoimidazo[2,1-a]isoquinolines
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A one-pot protocol toward several substituted 5,6-dihydrobenzo[4,5] imidazo[2,1-a]isoquinolines 1 starting with 2-allylbenzaldehydes 2 was described. The process was carried out the one-pot condensation/hydroamination reaction of substituted 2-allylbenzaldehydes 2 with 1,2-diaminobenzenes 3 in refluxing toluene in good yields. Skeleton 2 was prepared via one-pot ortho-metalative PhBCl2-mediated double alkylation of hydroxybenzaldehyde 4 with LDA in moderate yields.
- Chang, Meng-Yang,Wu, Ming-Hao,Chen, Yeh-Long
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scheme or table
p. 4156 - 4160
(2012/08/28)
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- Facile synthesis of substituted isoquinolines
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A facile three-step protocol toward methoxy isoquinolines 7 starting with substituted 2-allylbenzaldehydes 9 was described. The overall synthetic process of skeleton 7 was carried out using the Grignard addition, PCC-oxidation, and one-pot oxidative cleavage of the olefinic group of skeleton 9 with OsO 4-NaIO4 followed by the condensation of the resulting 1,5-dicarbonyl compounds with NH4OAc. Skeleton 9 was prepared in high yield via the known Claisen rearrangement of skeleton 8 and O-methylation. Papaverine 2 is also synthesized via the simple three-step synthetic protocol.
- Chang, Meng-Yang,Wu, Ming-Hao,Lee, Nein-Chia,Lee, Ming-Fang
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p. 2125 - 2128
(2012/07/14)
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- 1-(PIPERIDIN-4-YL)-1H-INDOLE DERIVATIVE
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The present invention provides a compound represented by the formula (1) or a pharmacologically acceptable salt thereof, or a hydrate thereof (provided that a compound in which all of R4a, R4b, and R4c are hydrogen atoms is excluded.): [wherein R1 represents a hydrogen atom, R2 represents a hydrogen atom, R3 represents the formula: wherein R4a, R4b, and R4c are the same as or different from each other and each represents a hydrogen atom, a C1-6 alkyl group or a C1-6 alkoxy group, etc.]
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Page/Page column 63
(2010/11/28)
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- The Intramolecular Asymmetric Pauson-Khand Cyclization As A Novel and General Stereoselective Route to Benzindene Prostacyclins: Synthesis of UT-15 (Treprostinil)
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A general and novel solution to the synthesis of biologically important stable analogues of prostacyclin PGI2, namely benzindene prostacyclins, has been achieved via the stereoselective intramolecular Pauson-Khand cyclization (PKC). This work illustrates for the first time the synthetic utility and reliability of the asymmetric PKC route for synthesis and subsequent manufacture of a complex drug substance on a multikilogram scale. The synthetic route surmounts issues of individual step stereoselectivity and scalability. The key step in the synthesis involves efficient stereoselection effected in the PKC of a benzoenyne under the agency of the benzylic OTBDMS group, which serves as a temporary stereodirecting group that is conveniently removed via benzylic hydrogenolysis concomitantly with the catalytic hydrogenation of the enone PKC product. Thus the benzylic chiral center dictates the subsequent stereochemistry of the stereogenic centers at three carbon atoms (C3a, C9a, and C1).
- Moriarty, Robert M.,Rani, Neena,Enache, Livia A.,Rao, Munagala S.,Batra, Hitesh,Guo, Liang,Penmasta, Raju A.,Staszewski, James P.,Tuladhar, Sudersan M.,Prakash, Om,Crich, David,Hirtopeanu, Anca,Gilardi, Richard
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p. 1890 - 1902
(2007/10/03)
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